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Guanosine monophosphate synthetase, () also known as GMPS is an
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 converts
xanthosine monophosphate
Xanthosine monophosphate also called Xanthylate is an intermediate in purine metabolism. It is a ribonucleoside monophosphate. It is formed from IMP via the action of IMP dehydrogenase, and it forms GMP via the action of GMP synthase. Also, XMP can ...
to
guanosine monophosphate
Guanosine monophosphate (GMP), also known as 5′-guanidylic acid or guanylic acid (conjugate base guanylate), is a nucleotide that is used as a monomer in RNA. It is an ester of phosphoric acid with the nucleoside guanosine. GMP consists of the ...
.
In the de novo synthesis of purine nucleotides, IMP is the branch point metabolite at which point the pathway diverges to the synthesis of either guanine or adenine nucleotides. In the guanine nucleotide pathway, there are 2 enzymes involved in converting IMP to GMP, namely IMP dehydrogenase (IMPD1), which catalyzes the oxidation of IMP to XMP, and GMP synthetase, which catalyzes the amination of XMP to GMP.
Enzymology
In
enzymology
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 ...
, a GMP synthetase (glutamine-hydrolysing) () is an
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
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 ...
the
chemical reaction
A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
:ATP + xanthosine 5'-phosphate +
L-glutamine + H
2O
AMP + diphosphate + GMP +
L-glutamate
The 4
substrates of this enzyme are
ATP
ATP may refer to:
Companies and organizations
* Association of Tennis Professionals, men's professional tennis governing body
* American Technical Publishers, employee-owned publishing company
* ', a Danish pension
* Armenia Tree Project, non ...
,
xanthosine 5'-phosphate,
L-glutamine, and
H2O, whereas its 4
products are
AMP #REDIRECT Amp #REDIRECT Amp
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{{Redirect category shell, {{R from other capitalisation{{R from ambiguous page ...
,
diphosphate,
GMP
GMP may refer to:
Finance and economics
* Gross metropolitan product
* Guaranteed maximum price
* Guaranteed Minimum Pension
Science and technology
* GNU Multiple Precision Arithmetic Library, a software library
* Granulocyte-macrophage progenit ...
, and
L-glutamate.
This enzyme belongs to the family of
ligases, specifically those forming carbon-nitrogen bonds carbon-nitrogen ligases with glutamine as amido-N-donor. The
systematic name of this enzyme class is xanthosine-5'-phosphate:
L-glutamine amido-ligase (AMP-forming). This enzyme participates in
purine metabolism
Purine metabolism refers to the metabolic pathways to synthesize and break down purines that are present in many organisms.
Biosynthesis
Purines are biologically synthesized as nucleotides and in particular as ribotides, i.e. bases attached to ri ...
and
glutamate metabolism
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 ...
. At least one compound,
Psicofuranin is known to
inhibit this enzyme.
Structural studies
As of late 2007, 5
structures have been solved for this class of enzymes, with
PDB accession codes , , , , and .
Role in metabolism
Purine metabolism
GMP synthase is the second step in the generation of
GMP
GMP may refer to:
Finance and economics
* Gross metropolitan product
* Guaranteed maximum price
* Guaranteed Minimum Pension
Science and technology
* GNU Multiple Precision Arithmetic Library, a software library
* Granulocyte-macrophage progenit ...
from IMP; the first step occurs when IMP dehydrogenase generates XMP, and then GMP synthetase is able to react with glutamine and ATP to generate GMP. IMP may also be generated into AMP by adenylosuccinate synthetase and then adenylosuccinate lyase.
Amino acid metabolism
GMP synthase is also involved in amino acid metabolism because it generates L-glutamate from L-glutamine.
Organismal involvement
This enzyme is widely distributed and a number of crystal structures have been solved, including in ''
Escherichia coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', ''
Pyrococcus Horikoshii
''Pyrococcus horikoshii'' is a hyperthermophilic, anaerobic archaeon, first isolated from hydrothermal fluid samples obtained at the Okinawa Trough vents at a depth of . It is obligately heterotrophic, cells are irregular cocci with a tuft of fl ...
'', ''
Thermoplasma acidophil'', ''
Homo sapiens
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
'', ''
Thermus thermophilus
''Thermus thermophilus'' is a Gram-negative bacterium used in a range of biotechnological applications, including as a model organism for genetic manipulation, structural genomics, and systems biology. The bacterium is extremely thermophilic, w ...
'' and ''
Mycobacterium tuberculosis
''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae and the causative agent of tuberculosis. First discovered in 1882 by Robert Koch, ''M. tuberculosis'' has an unusual, waxy coating on its c ...
''. The most extensive structural studies have been done in
E. coli
''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
.
Structure and function
GMP synthase forms a
tetramer
A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
in an open box shape, which is a
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ( ...
of dimers. The R interfaces are held together with 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 ...
core and a
beta sheet
The beta sheet, (β-sheet) (also β-pleated sheet) is a common motif of the regular protein secondary structure. Beta sheets consist of beta strands (β-strands) connected laterally by at least two or three backbone hydrogen bonds, forming a g ...
, while the P
dimer
Dimer may refer to:
* Dimer (chemistry), a chemical structure formed from two similar sub-units
** Protein dimer, a protein quaternary structure
** d-dimer
* Dimer model, an item in statistical mechanics, based on ''domino tiling''
* Julius Dimer ( ...
interfaces do not have 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 ...
core and are more variable than the R interfaces.
This enzyme also binds several
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, including
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 ...
,
pyrophosphate,
AMP #REDIRECT Amp #REDIRECT Amp
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,