GMP synthase

Guanosine monophosphate synthetase, (EC 6.3.5.2) also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

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, a GMP synthetase (glutamine-hydrolysing) (EC 6.3.5.2) is an enzyme that catalyzes the chemical reaction

ATP + xanthosine 5'-phosphate + L-glutamine + H2O

⇌

{\displaystyle \rightleftharpoons }

AMP + diphosphate + GMP + L-glutamate

The 4 substrates of this enzyme are ATP, xanthosine 5'-phosphate, L-glutamine, and H2O, whereas its 4 products are AMP, diphosphate, GMP, 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 and glutamate metabolism. 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 PDB: 1GPM​, PDB: 1WL8​, PDB: 2A9V​, PDB: 2D7J​, and PDB: 2DPL​.

Role in metabolism

Purine metabolism

GMP synthase is the second step in the generation of GMP 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.