Cytochrome P450 Aromatic O-demethylase on:
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Cytochrome P450 aromatic O-demethylase is a bacterial
CcoA and GcoB are closely interlinked, acting as an heterodimer in solution. The surface of GcoB has an acidic patch that must interact with the matching basic region in GcoA. It is assumed that the part of GcoB interacting with GcoA is at the intersection between the FAD binding domain and ferredoxin domain. To achieve this GcoB would have to go through some structural change, which would represent a new class of P450 systems (family N).
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 ...
that catalyzes the demethylation of lignin
Lignin is a class of complex organic polymers that form key structural materials in the support tissues of most plants. Lignins are particularly important in the formation of cell walls, especially in wood and bark, because they lend rigidity ...
and various lignols. The net reaction follows the following stoichiometry, illustrated with a generic methoxy arene:
:ArOCH3 + O2 + 2e− + 2H+ → ArOH + CH2O + H2O
The enzyme is notable for its promiscuity, it effects the O-demethylation of a range of substrates, including lignin.
It is a heterodimeric
In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...
protein derived from the products of two genes. The component proteins are a 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 ...
enzyme (encoded by the gcoA gene from the family CYP255A) and a three-domain reductase
A reductase is an enzyme that catalyzes a reduction reaction.
Examples
* 5α-Reductase
* 5β-Reductase
* Dihydrofolate reductase
* HMG-CoA reductase
* Methemoglobin reductase
* Ribonucleotide reductase
* Thioredoxin reductase
* ''E. coli'' ...
(encoded by the gcoB gene) complexed with three cofactors
Cofactor may also refer to:
* Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed
* A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...
( 2Fe-2S, FAD
A fad or trend is any form of collective behavior that develops within a culture, a generation or social group in which a group of people enthusiastically follow an impulse for a short period.
Fads are objects or behaviors that achieve short- ...
, and NADH
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
).
Mechanism
GcoA and GcoB form a dimer complex in solution. GcoA process the substrate while GcoB provides the electrons to support the mixed function oxidase. As with other P450's, monooxygenation of the substrate proceeds concomitantly with reduction of half an equivalent of O2 to water. Anoxygen rebound mechanism
In biochemistry, the oxygen rebound mechanism is the pathway for hydroxylation of organic compounds by iron-containing oxygenases. Many enzymes effect the hydroxylation of hydrocarbons as a means for biosynthesis, detoxification, gene regulation, ...
can be assumed. GcoA positions the aromatic ring within the hydrophobic active site cavity where the heme is located.
Structure
GcoA has a typical P450 structure: a thiolate-ligated heme next to a buried active site. GcoB is however unusual. Cytochrome P450s normally are complemented by either a cytochrome P450 reductase or a ferredoxin and ferredoxin reductase; its electrons are carried byNAD+
Nicotinamide adenine dinucleotide (NAD) is a coenzyme central to metabolism. Found in all living cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an aden ...
or NADP+
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a Cofactor (biochemistry), cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid synth ...
. GcoB however has a single polypeptide. This polypeptide has an N-terminal ferredoxin with both an NAD(P)+ and also an FAD
A fad or trend is any form of collective behavior that develops within a culture, a generation or social group in which a group of people enthusiastically follow an impulse for a short period.
Fads are objects or behaviors that achieve short- ...
binding region.
CcoA and GcoB are closely interlinked, acting as an heterodimer in solution. The surface of GcoB has an acidic patch that must interact with the matching basic region in GcoA. It is assumed that the part of GcoB interacting with GcoA is at the intersection between the FAD binding domain and ferredoxin domain. To achieve this GcoB would have to go through some structural change, which would represent a new class of P450 systems (family N).
Potential applications
Cytochrome P450 aromatic O-demethylase assists in the partial O-demethylation of lignin. The resulting 1,2-diols are well suited for oxidative degradation via intra- and extra-diol dioxygenases. Thus O-demethylated lignins are potentially susceptible to partial depolymerization. With fewer crosslinks, the modified ligand is potentially more useful than the precursor., ranging from fuelsReferences
{{Cytochrome P450 Cytochrome P450 EC 1.14.14 EC 1.6.2 Prokaryote genes