Metalloprotein is a generic term for a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that contains a metal ion
cofactor.
A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-binding
protein domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
s although there may be up to 3000 human zinc metalloproteins.
Abundance
It is estimated that approximately half of all
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s contain a
metal
A metal (from Greek μέταλλον ''métallon'', "mine, quarry, metal") is a material that, when freshly prepared, polished, or fractured, shows a lustrous appearance, and conducts electricity and heat relatively well. Metals are typicall ...
. In another estimate, about one quarter to one third of all proteins are proposed to require metals to carry out their functions. Thus, metalloproteins have many different functions in
cells, such as storage and transport of proteins,
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s and
signal transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...
proteins, or infectious diseases. The abundance of metal binding proteins may be inherent to the amino acids that proteins use, as even artificial proteins without evolutionary history will readily bind metals.
Most metals in the
human body
The human body is the structure of a Human, human being. It is composed of many different types of Cell (biology), cells that together create Tissue (biology), tissues and subsequently organ systems. They ensure homeostasis and the life, viabi ...
are bound to proteins. For instance, the relatively high concentration of iron in the human body is mostly due to the iron in
hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
.
Coordination chemistry principles
In metalloproteins, metal ions are usually coordinated by
nitrogen
Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at se ...
,
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
or
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
centers belonging to
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
residues of the protein. These donor groups are often provided by side-chains on the amino acid residues. Especially important are the
imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
substituent in
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
residues,
thiolate
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl grou ...
substituents in
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
residues, and
carboxylate
In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge.
Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...
groups provided by
aspartate
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
. Given the diversity of the metallo
proteome
The proteome is the entire set of proteins that is, or can be, expressed by a genome, cell, tissue, or organism at a certain time. It is the set of expressed proteins in a given type of cell or organism, at a given time, under defined conditions. ...
, virtually all amino acid residues have been shown to bind metal centers. The peptide backbone also provides donor groups; these include deprotonated
amide
In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it is ...
s and the amide
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
oxygen centers. Lead(II) binding in natural and artificial proteins has been reviewed.
In addition to donor groups that are provided by amino acid residues, many organic
cofactors function as ligands. Perhaps most famous are the tetradentate N
4 macrocyclic
Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry.
...
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
s incorporated into the
heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consisti ...
protein. Inorganic ligands such as sulfide and oxide are also common.
Storage and transport metalloproteins
These are the second stage product of protein hydrolysis obtained by treatment with slightly stronger acids and alkalies.
Oxygen carriers
Hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
, which is the principal oxygen-carrier in humans, has four subunits in which the
iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
(II) ion is coordinated by the planar
macrocyclic
Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry.
...
ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
protoporphyrin IX
Protoporphyrin IX is an organic compound, classified as a porphyrin, that plays an important role in living organisms as a precursor to other critical compounds like heme (hemoglobin) and chlorophyll. It is a deeply colored solid that is not sol ...
(PIX) and the
imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
nitrogen atom of a
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
residue. The sixth coordination site contains a
water
Water (chemical formula ) is an inorganic, transparent, tasteless, odorless, and nearly colorless chemical substance, which is the main constituent of Earth's hydrosphere and the fluids of all known living organisms (in which it acts as a ...
molecule or a
dioxygen
There are several known allotropes of oxygen. The most familiar is molecular oxygen (O2), present at significant levels in Earth's atmosphere and also known as dioxygen or triplet oxygen. Another is the highly reactive ozone (O3). Others are:
*A ...
molecule. By contrast the protein
myoglobin
Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...
, found in
muscle cell
A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...
s, has only one such unit. The active site is located in a
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, th ...
pocket. This is important as without it the iron(II) would be irreversibly
oxidized
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
to iron(III). The
equilibrium constant
The equilibrium constant of a chemical reaction is the value of its reaction quotient at chemical equilibrium, a state approached by a dynamic chemical system after sufficient time has elapsed at which its composition has no measurable tendency ...
for the formation of HbO
2 is such that oxygen is taken up or released depending on the
partial pressure
In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal gas ...
of oxygen in the
lung
The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s or in muscle. In hemoglobin the four subunits show a cooperativity effect that allows for easy oxygen transfer from hemoglobin to myoglobin.
[
In both ]hemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
and myoglobin
Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...
it is sometimes incorrectly stated that the oxygenated species contains iron(III). It is now known that the diamagnetic
Diamagnetic materials are repelled by a magnetic field; an applied magnetic field creates an induced magnetic field in them in the opposite direction, causing a repulsive force. In contrast, paramagnetic and ferromagnetic materials are attracted ...
nature of these species is because the iron(II) atom is in the low-spin Spin states when describing transition metal coordination complexes refers to the potential spin configurations of the central metal's d electrons. For several oxidation states, metals can adopt high-spin and low-spin configurations. The ambiguity o ...
state. In oxyhemoglobin
Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyte ...
the iron atom is located in the plane of the porphyrin ring, but in the paramagnetic
Paramagnetism is a form of magnetism whereby some materials are weakly attracted by an externally applied magnetic field, and form internal, induced magnetic fields in the direction of the applied magnetic field. In contrast with this behavior, d ...
deoxyhemoglobin the iron atom lies above the plane of the ring.[ Fig.25.7, p 1100 illustrates the structure of deoxyhemoglobin] This change in spin state is a cooperative effect due to the higher crystal field splitting Crystal field theory (CFT) describes the breaking of degenerate energy levels, degeneracies of electron orbital states, usually ''d'' or ''f'' orbitals, due to a static electric field produced by a surrounding charge distribution (anion neighbors). ...
and smaller ionic radius
Ionic radius, ''r''ion, is the radius of a monatomic ion in an ionic crystal structure. Although neither atoms nor ions have sharp boundaries, they are treated as if they were hard spheres with radii such that the sum of ionic radii of the cation ...
of Fe2+ in the oxyhemoglobin moiety.
Hemerythrin
Hemerythrin (also spelled haemerythrin; grc, αἷμα, haîma, blood, grc, ἐρυθρός, erythrós, red) is an oligomeric protein responsible for oxygen (O2) transport in the marine invertebrate phyla of sipunculids, priapulids, brachiop ...
is another iron-containing oxygen carrier. The oxygen binding site is a binuclear iron center. The iron atoms are coordinated to the protein through the carboxylate
In organic chemistry, a carboxylate is the conjugate base of a carboxylic acid, (or ). It is an ion with negative charge.
Carboxylate salts are salts that have the general formula , where M is a metal and ''n'' is 1, 2,...; ''carboxylat ...
side chains of a glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...
and aspartate
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
and five histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
residues. The uptake of O2 by hemerythrin is accompanied by two-electron oxidation of the reduced binuclear center to produce bound peroxide
In chemistry, peroxides are a group of compounds with the structure , where R = any element. The group in a peroxide is called the peroxide group or peroxo group. The nomenclature is somewhat variable.
The most common peroxide is hydrogen p ...
(OOH−). The mechanism of oxygen uptake and release have been worked out in detail.
Hemocyanin
Hemocyanins (also spelled haemocyanins and abbreviated Hc) are proteins that transport oxygen throughout the bodies of some invertebrate animals. These metalloproteins contain two copper atoms that reversibly bind a single oxygen molecule (O2) ...
s carry oxygen in the blood of most mollusk
Mollusca is the second-largest phylum of invertebrate animals after the Arthropoda, the members of which are known as molluscs or mollusks (). Around 85,000 extant species of molluscs are recognized. The number of fossil species is e ...
s, and some arthropod
Arthropods (, (gen. ποδός)) are invertebrate animals with an exoskeleton, a Segmentation (biology), segmented body, and paired jointed appendages. Arthropods form the phylum Arthropoda. They are distinguished by their jointed limbs and Arth ...
s such as the horseshoe crab
Horseshoe crabs are marine and brackish water arthropods of the family Limulidae and the only living members of the order Xiphosura. Despite their name, they are not true crabs or crustaceans: they are chelicerates, most closely related to arachn ...
. They are second only to hemoglobin in biological popularity of use in oxygen transport. On oxygenation the two copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
(I) atoms at the active site are oxidized to copper(II) and the dioxygen molecules are reduced to peroxide, .
Chlorocruorin (as the larger carrier erythrocruorin
Erythrocruorin (from Greek ''eruthros'' "red" + Latin ''cruor'' "blood"), and the similar chlorocruorin (from Greek ''khlōros'' "green" + Latin ''cruor'' "blood"), are large oxygen-carrying hemeprotein complexes, which have a molecular mass gre ...
) is an oxygen-binding hemeprotein present in the blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
of many annelid
The annelids (Annelida , from Latin ', "little ring"), also known as the segmented worms, are a large phylum, with over 22,000 extant species including ragworms, earthworms, and leeches. The species exist in and have adapted to various ecol ...
s, particularly certain marine polychaete
Polychaeta () is a paraphyletic class (biology), class of generally marine invertebrate, marine annelid worms, common name, commonly called bristle worms or polychaetes (). Each body segment has a pair of fleshy protrusions called parapodia that ...
s.
Cytochromes
Oxidation
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
and reduction reactions are not common in organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
as few organic molecules can act as oxidizing
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
or reducing agent
In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ).
Examples of substances that are commonly reducing agents include the Earth meta ...
s. Iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
(II), on the other hand, can easily be oxidized to iron(III). This functionality is used in cytochrome
Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bin ...
s, which function as electron-transfer
Electron transfer (ET) occurs when an electron relocates from an atom or molecule to another such chemical entity. ET is a mechanistic description of certain kinds of redox reactions involving transfer of electrons.
Electrochemical processes ar ...
vectors. The presence of the metal ion allows metalloenzyme
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. A large proportion of all proteins are part of this category. For instance, at least 1000 human proteins (out of ~20,000) contain zinc-binding protein domains al ...
s to perform functions such as redox reaction
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...
s that cannot easily be performed by the limited set of functional group
In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the rest ...
s found in amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
s. The iron atom in most cytochromes is contained in a heme
Heme, or haem (pronounced / hi:m/ ), is a precursor to hemoglobin, which is necessary to bind oxygen in the bloodstream. Heme is biosynthesized in both the bone marrow and the liver.
In biochemical terms, heme is a coordination complex "consisti ...
group. The differences between those cytochromes lies in the different side-chains. For instance cytochrome a has a heme a
Heme A (or haem A) is a heme, a coordination complex consisting of a macrocyclic ligand called a porphyrin, chelating an iron atom. Heme A is a biomolecule and is produced naturally by many organisms. Heme A, often appears a dichroic green/red wh ...
prosthetic group and cytochrome b has a heme b prosthetic group. These differences result in different Fe2+/Fe3+ redox potential
Redox potential (also known as oxidation / reduction potential, ''ORP'', ''pe'', ''E_'', or E_) is a measure of the tendency of a chemical species to acquire electrons from or lose electrons to an electrode and thereby be reduced or oxidised respe ...
s such that various cytochromes are involved in the mitochondrial
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
electron transport chain.
Cytochrome P450
Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...
enzymes perform the function of inserting an oxygen atom into a C−H bond, an oxidation reaction.
Rubredoxin
Rubredoxin
Rubredoxins are a class of low-molecular-weight iron-containing proteins found in sulfur-metabolizing bacteria and archaea. Sometimes rubredoxins are classified as iron-sulfur proteins; however, in contrast to iron-sulfur proteins, rubredoxins d ...
is an electron-carrier found in sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
-metabolizing bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and archaea
Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...
. The active site contains an iron ion coordinated by the sulfur atoms of four cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
residues forming an almost regular tetrahedron
In geometry, a tetrahedron (plural: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular faces, six straight edges, and four vertex corners. The tetrahedron is the simplest of all the o ...
. Rubredoxins perform one-electron transfer processes. The oxidation state
In chemistry, the oxidation state, or oxidation number, is the hypothetical charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...
of the iron atom changes between the +2 and +3 states. In both oxidation states the metal is high spin Spin states when describing transition metal coordination complexes refers to the potential spin configurations of the central metal's d electrons. For several oxidation states, metals can adopt high-spin and low-spin configurations. The ambiguity o ...
, which helps to minimize structural changes.
Plastocyanin
200px, The copper site in ">plastocyanin
Plastocyanin is one of the family of blue copper proteins
Copper proteins are proteins that contain one or more copper ions as prosthetic groups. Copper proteins are found in all forms of air-breathing life. These proteins are usually associated with electron-transfer with or without the involvement of ...
that are involved in electron transfer
Electron transfer (ET) occurs when an electron relocates from an atom or molecule to another such chemical entity. ET is a mechanistic description of certain kinds of redox reactions involving transfer of electrons.
Electrochemical processes ar ...
reactions. The copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
-binding site is described as distorted trigonal pyramidal
In chemistry, a trigonal pyramid is a molecular geometry with one atom at the apex and three atoms at the corners of a trigonal base, resembling a tetrahedron (not to be confused with the tetrahedral geometry). When all three atoms at the corner ...
. The trigonal plane of the pyramidal base is composed of two nitrogen atoms (N1 and N2) from separate histidines and a sulfur (S1) from a cysteine. Sulfur (S2) from an axial methionine forms the apex. The distortion occurs in the bond lengths between the copper and sulfur ligands. The Cu−S1 contact is shorter (207 pm) than Cu−S2 (282 pm).
The elongated Cu−S2 bonding destabilizes the Cu(II) form and increases the redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
potential of the protein. The blue color (597 nm peak absorption) is due to the Cu−S1 bond where S(pπ) to Cu(d''x''2−''y''2) charge transfer occurs.
In the reduced form of plastocyanin, His
His or HIS may refer to:
Computing
* Hightech Information System, a Hong Kong graphics card company
* Honeywell Information Systems
* Hybrid intelligent system
* Microsoft Host Integration Server
Education
* Hangzhou International School, in ...
-87 will become protonated with a p''K''a of 4.4. Protonation
In chemistry, protonation (or hydronation) is the adding of a proton (or hydron, or hydrogen cation), (H+) to an atom, molecule, or ion, forming a conjugate acid. (The complementary process, when a proton is removed from a Brønsted–Lowry acid, ...
prevents it acting as a ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electr ...
and the copper site geometry becomes trigonal planar
In chemistry, trigonal planar is a molecular geometry model with one atom at the center and three atoms at the corners of an equilateral triangle, called peripheral atoms, all in one plane. In an ideal trigonal planar species, all three ligands a ...
.
Metal-ion storage and transfer
Iron
Iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
is stored as iron(III) in ferritin
Ferritin is a universal intracellular protein that stores iron and releases it in a controlled fashion. The protein is produced by almost all living organisms, including archaea, bacteria, algae, higher plants, and animals. It is the primary ' ...
. The exact nature of the binding site has not yet been determined. The iron appears to be present as a hydrolysis
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
product such as FeO(OH). Iron is transported by transferrin
Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...
whose binding site consists of two tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
s, one aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
and one histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
. The human body has no mechanism for iron excretion. This can lead to iron overload
Iron overload or hemochromatosis (also spelled ''haemochromatosis'' in British English) indicates increased total accumulation of iron in the body from any cause and resulting organ damage. The most important causes are hereditary haemochromatosi ...
problems in patients treated with blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
s, as, for instance, with β-thalassemia
Thalassemias are inherited blood disorders characterized by decreased hemoglobin production. Symptoms depend on the type and can vary from none to severe. Often there is mild to severe anemia (low red blood cells or hemoglobin). Anemia can result ...
. Iron is actually excreted in urine and is also concentrated in bile which is excreted in feces.
Copper
Ceruloplasmin is the major copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
-carrying protein in the blood. Ceruloplasmin exhibits oxidase activity, which is associated with possible oxidation of Fe(II) into Fe(III), therefore assisting in its transport in the blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intra ...
in association with transferrin, which can carry iron only in the Fe(III) state.
Calcium
Osteopontin is involved in mineralization in the extracellular matrices of bones and teeth.
Metalloenzymes
Metalloenzymes all have one feature in common, namely that the metal ion is bound to the protein with one labile
Lability refers to something that is constantly undergoing change or is likely to undergo change.
Biochemistry
In reference to biochemistry, this is an important concept as far as kinetics is concerned in metalloproteins. This can allow for th ...
coordination site. As with all enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s, the shape of the active site
In biology and biochemistry, the active site is the region of an enzyme where substrate molecules bind and undergo a chemical reaction. The active site consists of amino acid residues that form temporary bonds with the substrate (binding site) a ...
is crucial. The metal ion is usually located in a pocket whose shape fits the substrate. The metal ion catalyzes reactions that are difficult to achieve in organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, J.; ...
.
Carbonic anhydrase
In aqueous solution
An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, or sodium chloride (NaCl), in water would be re ...
, carbon dioxide
Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...
forms carbonic acid
:CO2 + H2O H2CO3
This reaction is very slow in the absence of a catalyst, but quite fast in the presence of the hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and hydrogen atom held together by a single covalent bond, and carries a negative electric charge. It is an important but usually minor constituent of water. I ...
ion
:CO2 + OH−
A reaction similar to this is almost instantaneous with carbonic anhydrase
The carbonic anhydrases (or carbonate dehydratases) () form a family of enzymes that catalyze the interconversion between carbon dioxide and water and the dissociated ions of carbonic acid (i.e. bicarbonate and hydrogen ions). The active site ...
. The structure of the active site in carbonic anhydrases is well known from a number of crystal structures. It consists of a zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
ion coordinated by three imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
nitrogen atoms from three histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
units. The fourth coordination site is occupied by a water molecule. The coordination sphere of the zinc ion is approximately tetrahedral
In geometry, a tetrahedron (plural: tetrahedra or tetrahedrons), also known as a triangular pyramid, is a polyhedron composed of four triangular faces, six straight edges, and four vertex corners. The tetrahedron is the simplest of all the o ...
. The positively-charged zinc ion polarizes the coordinated water molecule, and nucleophilic
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
attack by the negatively-charged hydroxide portion on carbon dioxide proceeds rapidly. The catalytic cycle produces the bicarbonate ion and the hydrogen ion[ as the equilibrium
:H2CO3 + H+
favours dissociation of carbonic acid at biological pH values.]
Vitamin B12-dependent enzymes
The cobalt
Cobalt is a chemical element with the symbol Co and atomic number 27. As with nickel, cobalt is found in the Earth's crust only in a chemically combined form, save for small deposits found in alloys of natural meteoric iron. The free element, pr ...
-containing Vitamin B12 (also known as cobalamin) catalyzes the transfer of methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...
(−CH3) groups between two molecules, which involves the breaking of C−C bonds, a process that is energetically expensive in organic reactions. The metal ion lowers the activation energy
In chemistry and physics, activation energy is the minimum amount of energy that must be provided for compounds to result in a chemical reaction. The activation energy (''E''a) of a reaction is measured in joules per mole (J/mol), kilojoules pe ...
for the process by forming a transient Co−CH3 bond. The structure of the coenzyme
A cofactor is a non-protein chemical compound or metallic ion that is required for an enzyme's role as a catalyst (a catalyst is a substance that increases the rate of a chemical reaction). Cofactors can be considered "helper molecules" that ass ...
was famously determined by Dorothy Hodgkin
Dorothy Mary Crowfoot Hodgkin (née Crowfoot; 12 May 1910 – 29 July 1994) was a Nobel Prize-winning British chemist who advanced the technique of X-ray crystallography to determine the structure of biomolecules, which became essential fo ...
and co-workers, for which she received a Nobel Prize in Chemistry
)
, image = Nobel Prize.png
, alt = A golden medallion with an embossed image of a bearded man facing left in profile. To the left of the man is the text "ALFR•" then "NOBEL", and on the right, the text (smaller) "NAT•" then "M ...
. It consists of a cobalt(II) ion coordinated to four nitrogen atoms of a corrin
Corrin is a heterocyclic compound. It is the parent macrocycle related to the substituted derivative that is found in vitamin B12. Its name reflects that it is the "core" of vitamin B12 (cobalamins).Nelson, D. L.; Cox, M. M. "Lehninger, Princ ...
ring and a fifth nitrogen atom from an imidazole
Imidazole (ImH) is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole Diazole refers ...
group. In the resting state there is a Co−C sigma bond
In chemistry, sigma bonds (σ bonds) are the strongest type of covalent chemical bond. They are formed by head-on overlapping between atomic orbitals. Sigma bonding is most simply defined for diatomic molecules using the language and tools of s ...
with the 5′ carbon atom of adenosine
Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
. This is a naturally occurring organometallic
Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and so ...
compound, which explains its function in ''trans''-methylation reactions, such as the reaction carried out by methionine synthase
Methionine synthase also known as MS, MeSe, MTR is responsible for the regeneration of methionine from homocysteine. In humans it is encoded by the ''MTR'' gene (5-methyltetrahydrofolate-homocysteine methyltransferase). Methionine synthase forms ...
.
Nitrogenase (nitrogen fixation)
The fixation of atmospheric nitrogen is a very energy-intensive process, as it involves breaking the very stable triple bond
A triple bond in chemistry is a chemical bond between two atoms involving six bonding electrons instead of the usual two in a covalent single bond. Triple bonds are stronger than the equivalent single bonds or double bonds, with a bond order o ...
between the nitrogen atoms. The enzyme nitrogenase
Nitrogenases are enzymes () that are produced by certain bacteria, such as cyanobacteria (blue-green bacteria) and rhizobacteria. These enzymes are responsible for the Organic redox reaction, reduction of nitrogen (N2) to ammonia (NH3). Nitrog ...
is one of the few enzymes that can catalyze the process. The enzyme occurs in ''Rhizobium'' bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
. There are three components to its action: a molybdenum
Molybdenum is a chemical element with the symbol Mo and atomic number 42 which is located in period 5 and group 6. The name is from Neo-Latin ''molybdaenum'', which is based on Ancient Greek ', meaning lead, since its ores were confused with lea ...
atom at the active site, iron–sulfur clusters that are involved in transporting the electrons needed to reduce the nitrogen, and an abundant energy source in the form of magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
ATP. This last is provided by a mutualistic symbiosis between the bacteria and a host plant, often a legume
A legume () is a plant in the family Fabaceae (or Leguminosae), or the fruit or seed of such a plant. When used as a dry grain, the seed is also called a pulse. Legumes are grown agriculturally, primarily for human consumption, for livestock f ...
. The reaction may be written symbolically as
:N2 + 16 Mg ATP + 8 e− → 2 NH3 + 16 Mg ADP +16 Pi + H2
where Pi stands for inorganic phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phospho ...
. The precise structure of the active site has been difficult to determine. It appears to contain a MoFe7S8 cluster that is able to bind the dinitrogen molecule and, presumably, enable the reduction process to begin. The electrons are transported by the associated "P" cluster, which contains two cubical Fe4S4 clusters joined by sulfur bridges.
Superoxide dismutase
The superoxide
In chemistry, a superoxide is a compound that contains the superoxide ion, which has the chemical formula . The systematic name of the anion is dioxide(1−). The reactive oxygen ion superoxide is particularly important as the product of the ...
ion, is generated in biological systems by reduction of molecular oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...
. It has an unpaired electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no kn ...
, so it behaves as a free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
. It is a powerful oxidizing agent
An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or "Electron acceptor, accepts"/"receives" an electron from a (called the , , or ). In ot ...
. These properties render the superoxide ion very toxic
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...
and are deployed to advantage by phagocytes
Phagocytes are cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek ', "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek '' ...
to kill invading microorganism
A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s. Otherwise, the superoxide ion must be destroyed before it does unwanted damage in a cell. The superoxide dismutase
Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen me ...
enzymes perform this function very efficiently.
The formal oxidation state
In chemistry, the oxidation state, or oxidation number, is the hypothetical charge of an atom if all of its bonds to different atoms were fully ionic. It describes the degree of oxidation (loss of electrons) of an atom in a chemical compound. C ...
of the oxygen atoms is −. In solutions at neutral pH, the superoxide ion disproportionates
In chemistry, disproportionation, sometimes called dismutation, is a redox reaction in which one compound of intermediate oxidation state converts to two compounds, one of higher and one of lower oxidation states. More generally, the term can ...
to molecular oxygen and hydrogen peroxide
Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscous than water. It is used as an oxidizer, bleaching agent, and antiseptic, usually as a dilute solution (3% ...
.
:2 + 2 H+ → O2 + H2O2
In biology this type of reaction is called a dismutation
In chemistry, disproportionation, sometimes called dismutation, is a redox reaction in which one compound of intermediate oxidation state converts to two compounds, one of higher and one of lower oxidation states. More generally, the term can b ...
reaction. It involves both oxidation and reduction of superoxide ions. The superoxide dismutase
Superoxide dismutase (SOD, ) is an enzyme that alternately catalyzes the dismutation (or partitioning) of the superoxide () radical into ordinary molecular oxygen (O2) and hydrogen peroxide (). Superoxide is produced as a by-product of oxygen me ...
(SOD) group of enzymes increase the rate of reaction
The reaction rate or rate of reaction is the speed at which a chemical reaction takes place, defined as proportional to the increase in the concentration of a product per unit time and to the decrease in the concentration of a reactant per unit ...
to near the diffusion-limited rate. The key to the action of these enzymes is a metal ion with variable oxidation state that can act either as an oxidizing agent or as a reducing agent.
:Oxidation: M(''n''+1)+ + → M''n''+ + O2
:Reduction: M''n''+ + + 2 H+ → M(''n''+1)+ + H2O2.
In human SOD the active metal is copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
, as Cu(II) or Cu(I), coordinated tetrahedrally by four histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the de ...
residues. This enzyme also contains zinc
Zinc is a chemical element with the symbol Zn and atomic number 30. Zinc is a slightly brittle metal at room temperature and has a shiny-greyish appearance when oxidation is removed. It is the first element in group 12 (IIB) of the periodi ...
ions for stabilization and is activated by copper chaperone for superoxide dismutase ( CCS). Other isozyme In biochemistry, isozymes (also known as isoenzymes or more generally as multiple forms of enzymes) are enzymes that differ in amino acid sequence but catalyze the same chemical reaction. Isozymes usually have different kinetic parameters (e.g. dif ...
s may contain iron
Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...
, manganese or nickel
Nickel is a chemical element with symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel is a hard and ductile transition metal. Pure nickel is chemically reactive but large pieces are slow to ...
. Ni-SOD is particularly interesting as it involves nickel(III), an unusual oxidation state for this element. The active site nickel geometry cycles from square planar
The square planar molecular geometry in chemistry describes the stereochemistry (spatial arrangement of atoms) that is adopted by certain chemical compounds. As the name suggests, molecules of this geometry have their atoms positioned at the corne ...
Ni(II), with thiolate (Cys2 and Cys6) and backbone nitrogen (His1 and Cys2) ligands, to square pyramidal
In molecular geometry, square pyramidal geometry describes the shape of certain Chemical compound, compounds with the formula where L is a ligand. If the ligand atoms were connected, the resulting shape would be that of a Square pyramid, pyram ...
Ni(III) with an added axial His1 side chain ligand.
Chlorophyll-containing proteins
Chlorophyll plays a crucial role in photosynthesis
Photosynthesis is a process used by plants and other organisms to convert light energy into chemical energy that, through cellular respiration, can later be released to fuel the organism's activities. Some of this chemical energy is stored i ...
. It contains a magnesium
Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...
enclosed in a chlorin
In organic chemistry, chlorins are tetrapyrrole pigments that are partially hydrogenated porphyrins. The parent chlorin is an unstable compound which undergoes air oxidation to porphine.
The name chlorin derives from chlorophyll. Chlorophylls a ...
ring. However, the magnesium ion is not directly involved in the photosynthetic function and can be replaced by other divalent ions with little loss of activity. Rather, the photon
A photon () is an elementary particle that is a quantum of the electromagnetic field, including electromagnetic radiation such as light and radio waves, and the force carrier for the electromagnetic force. Photons are massless, so they always ...
is absorbed by the chlorin ring, whose electronic structure is well-adapted for this purpose.
Initially, the absorption of a photon causes an electron
The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family,
and are generally thought to be elementary particles because they have no kn ...
to be excited into a singlet state
In quantum mechanics, a singlet state usually refers to a system in which all electrons are paired. The term 'singlet' originally meant a linked set of particles whose net angular momentum is zero, that is, whose overall spin quantum number s=0. A ...
of the Q band. The excited state
In quantum mechanics, an excited state of a system (such as an atom, molecule or nucleus) is any quantum state of the system that has a higher energy than the ground state (that is, more energy than the absolute minimum). Excitation refers to a ...
undergoes an intersystem crossing Intersystem crossing (ISC) is an isoenergetic radiationless process involving a transition between the two electronic states with different spin multiplicity.
Excited Singlet and Triplet States
When an electron in a molecule with a singlet ground ...
from the singlet state to a triplet state
In quantum mechanics, a triplet is a quantum state of a system with a spin of quantum number =1, such that there are three allowed values of the spin component, = −1, 0, and +1.
Spin, in the context of quantum mechanics, is not a mechanical ...
in which there are two electrons with parallel spin
Spin or spinning most often refers to:
* Spinning (textiles), the creation of yarn or thread by twisting fibers together, traditionally by hand spinning
* Spin, the rotation of an object around a central axis
* Spin (propaganda), an intentionally b ...
. This species is, in effect, a free radical
A daughter category of ''Ageing'', this category deals only with the biological aspects of ageing.
Ageing
Ailments of unknown cause
Biogerontology
Biological processes
Causes of death
Cellular processes
Gerontology
Life extension
Metabo ...
, and is very reactive and allows an electron to be transferred to acceptors that are adjacent to the chlorophyll in the chloroplast
A chloroplast () is a type of membrane-bound organelle known as a plastid that conducts photosynthesis mostly in plant and algal cells. The photosynthetic pigment chlorophyll captures the energy from sunlight, converts it, and stores it in ...
. In the process chlorophyll is oxidized. Later in the photosynthetic cycle, chlorophyll is reduced back again. This reduction ultimately draws electrons from water, yielding molecular oxygen as a final oxidation product.
Hydrogenase
Hydrogenases are subclassified into three different types based on the active site metal content: iron–iron hydrogenase, nickel–iron hydrogenase, and iron hydrogenase.
All hydrogenases catalyze reversible H2 uptake, but while the eFe
Agencia EFE, S.A. () is a Spanish international news agency, the major multimedia news agency in Spanish language and the world's fourth largest wire service after the Associated Press, Reuters, and Agence France-Presse. EFE was created in 1939 ...
and iFehydrogenases are true redox
Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate (chemistry), substrate change. Oxidation is the loss of Electron, electrons or an increase in the oxidation state, while reduction ...
catalysts
Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
, driving H2 oxidation and H+ reduction
:H2 2 H+ + 2 e−
the ehydrogenases catalyze the reversible heterolytic cleavage of H2.
:H2 H+ + H−
Ribozyme and deoxyribozyme
Since discovery of ribozyme
Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonst ...
s by Thomas Cech
Thomas Robert Cech (born December 8, 1947) is an American chemist who shared the 1989 Nobel Prize in Chemistry with Sidney Altman, for their discovery of the catalytic properties of RNA. Cech discovered that RNA could itself cut strands of RNA, ...
and Sidney Altman
Sidney Altman (May 7, 1939 – April 5, 2022) was a Canadian-American molecular biologist, who was the Sterling Professor of Molecular, Cellular, and Developmental Biology and Chemistry at Yale University. In 1989, he shared the Nobel Prize in ...
in the early 1980s, ribozymes have been shown to be a distinct class of metalloenzymes. Many ribozymes require metal ions in their active sites for chemical catalysis; hence they are called metalloenzymes. Additionally, metal ions are essential for structural stabilization of ribozymes. Group I intron
Group I introns are large self-splicing ribozymes. They catalyze their own excision from mRNA, tRNA and rRNA precursors in a wide range of organisms. The core secondary structure consists of nine paired regions (P1-P9). These fold to essentially ...
is the most studied ribozyme which has three metals participating in catalysis. Other known ribozymes include group II intron
Group II introns are a large class of self-catalytic ribozymes and mobile genetic elements found within the genes of all three domains of life. Ribozyme activity (e.g., self- splicing) can occur under high-salt conditions ''in vitro''. However, ...
, RNase P
Ribonuclease P (, ''RNase P'') is a type of ribonuclease which cleaves RNA. RNase P is unique from other RNases in that it is a ribozyme – a ribonucleic acid that acts as a catalyst in the same way that a protein-based enzyme would. Its fu ...
, and several small viral ribozymes (such as hammerhead, hairpin
A hairpin or hair pin is a long device used to hold a person's hair in place. It may be used simply to secure long hair out of the way for convenience or as part of an elaborate hairstyle or coiffure. The earliest evidence for dressing the hai ...
, HDV
HDV is a format for recording of high-definition video on DV cassette tape. The format was originally developed by JVC and supported by Sony, Canon, and Sharp. The four companies formed the HDV Consortium in September 2003.
Conceived as an af ...
, and VS) and the large subunit of ribosomes. Recently, four new classes of ribozymes have been discovered (named twister
Twister may refer to:
Weather
* Tornado
Aviation
* Pipistrel Twister, a Slovenian ultralight trike
* Silence Twister, a German homebuilt aircraft design
* Wings of Change Twister, an Austrian paraglider design
Entertainment
* ''Twister'' (1989 ...
, twister sister, pistol and hatchet) which are all self-cleaving ribozymes.
Deoxyribozyme
Deoxyribozymes, also called DNA enzymes, DNAzymes, or catalytic DNA, are DNA oligonucleotides that are capable of performing a specific chemical reaction, often but not always catalytic. This is similar to the action of other biological enzymes, ...
s, also called DNAzymes or catalytic DNA, are artificial catalytic DNA molecules that were first produced in 1994 and gained a rapid increase of interest since then. Almost all DNAzymes require metal ions in order to function; thus they are classified as metalloenzymes. Although ribozymes mostly catalyze cleavage of RNA substrates, a variety of reactions can be catalyzed by DNAzymes including RNA/DNA cleavage, RNA/DNA ligation, amino acid phosphorylation and dephosphorylation, and carbon–carbon bond formation. Yet, DNAzymes that catalyze RNA cleavage reaction are the most extensively explored ones. 10-23 DNAzyme, discovered in 1997, is one of the most studied catalytic DNAs with clinical applications as a therapeutic agent. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead
Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cu ...
-specific), the CA1-3 DNAzymes (copper
Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkis ...
-specific), the 39E DNAzyme (uranyl
The uranyl ion is an oxycation of uranium in the oxidation state +6, with the chemical formula . It has a linear structure with short U–O bonds, indicative of the presence of multiple bonds between uranium and oxygen. Four or more ligands may ...
-specific) and the NaA43 DNAzyme (sodium
Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable iso ...
-specific).
Signal-transduction metalloproteins
Calmodulin
300px, EF-hand motif
Calmodulin
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...
is an example of a signal-transduction protein. It is a small protein that contains four EF-hand
The EF hand is a helix–loop–helix structural domain or ''motif'' found in a large family of calcium-binding proteins.
The EF-hand motif contains a helix–loop–helix topology, much like the spread thumb and forefinger of the human hand, in ...
motifs, each of which is able to bind a Ca2+ ion.
In an EF-hand loop the calcium ion is coordinated in a pentagonal bipyramidal configuration. Six glutamic acid
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
and aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
residues involved in the binding are in positions 1, 3, 5, 7 and 9 of the polypeptide chain. At position 12, there is a glutamate or aspartate ligand that behaves as a (bidentate ligand), providing two oxygen atoms. The ninth residue in the loop is necessarily glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...
due to the conformational requirements of the backbone. The coordination sphere of the calcium ion contains only carboxylate oxygen atoms and no nitrogen atoms. This is consistent with the hard
Hard may refer to:
* Hardness, resistance of physical materials to deformation or fracture
* Hard water, water with high mineral content
Arts and entertainment
* ''Hard'' (TV series), a French TV series
* Hard (band), a Hungarian hard rock supe ...
nature of the calcium ion.
The protein has two approximately symmetrical domains, separated by a flexible "hinge" region. Binding of calcium causes a conformational change to occur in the protein. Calmodulin participates in an intracellular signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
system by acting as a diffusible second messenger to the initial stimuli.
Troponin
In both cardiac
The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...
and skeletal muscles
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
, muscular force production is controlled primarily by changes in the intracellular calcium
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
concentration
In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', ''number concentration'', an ...
. In general, when calcium rises, the muscles contract and, when calcium falls, the muscles relax. Troponin
image:Troponin Ribbon Diagram.png, 400px, Ribbon representation of the human cardiac troponin core complex (52 kDa core) in the calcium-saturated form. Blue = troponin C; green = troponin I; magenta = troponin T.; ; rendered with PyMOL
Troponin, ...
, along with actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...
and tropomyosin
Tropomyosin is a two-stranded alpha-helical, coiled coil protein found in actin-based cytoskeletons.
Tropomyosin and the actin skeleton
All organisms contain organelles that provide physical integrity to their cells. These type of organelles ar ...
, is the protein complex to which calcium binds to trigger the production of muscular force.
Transcription factors
Many transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...
s contain a structure known as a zinc finger
A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized struct ...
, this is a structural module where a region of protein folds around a zinc ion. The zinc does not directly contact the DNA that these proteins bind to. Instead, the cofactor is essential for the stability of the tightly folded protein chain. In these proteins, the zinc ion is usually coordinated by pairs of cysteine and histidine side-chains.
Other metalloenzymes
There are two types of carbon monoxide dehydrogenase
In enzymology, carbon monoxide dehydrogenase (CODH) () is an enzyme that catalyzes the chemical reaction
:CO + H2O + A \rightleftharpoons CO2 + AH2
The chemical process catalyzed by carbon monoxide dehydrogenase is similar to the water-gas shif ...
: one contains iron and molybdenum, the other contains iron and nickel. Parallels and differences in catalytic strategies have been reviewed.
Pb2+ (lead) can replace Ca2+ (calcium) as, for example, with calmodulin
Calmodulin (CaM) (an abbreviation for calcium-modulated protein) is a multifunctional intermediate calcium-binding messenger protein expressed in all eukaryotic cells. It is an intracellular target of the secondary messenger Ca2+, and the bind ...
or Zn2+ (zinc) as with metallocarboxypeptidase
A metalloexopeptidase is a type of enzyme that acts as a metalloproteinase exopeptidase.
These enzymes have a catalytic mechanism involving a metal, often zinc. They function in molecular biology as agents that cut the terminal (or penultimate) p ...
s
Some other metalloenzymes are given in the following table, according to the metal involved.
See also
References
External links
*
Catherine Drennan's Seminar: Snapshots of Metalloproteins
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Medicinal inorganic chemistry
Bioinorganic chemistry