220.127.116.11 - GMP synthase (glutamine-hydrolyzing)
- GMP synthetase (glutamine-hydrolyzing).
ATP + H2O + L-glutamine + XMP = AMP + diphosphate + GMP + 2 H(+) + L-glutamate
There are no Cofactors for this Enzyme
The Class I glutamine amidotransferase an example of a single enzymatic reaction being catalysed by two modules, each responsible for a distinct component of the reaction. It catalyses the amination of the nucleotide precursor xanthosine 5'-monophosphate to form GMP in the de novo purine biosynthesis pathway. The amidotransferase domain is found in related enzymes of the purine, pyrimidine, tryptophan, arginine, histidine and folic acid pathways. This domain includes a conserved Cys-His-Glu triad, responsible for the abstraction of the amide nitrogen from glutamine.
Despite the apparent catalytic readiness of the GMP synthetase active site, the Class I aminotransferase domain is actually a very poor glutaminase in the absence of the substrates XMP and ATP, which is consistent with the biological role of this enzyme, in which the hydrolysis of glutamine is tightly couple with the formation of GMP. The synthetase domain catalyses the addition of ammonia to an acceptor substrate. They are designed to work in concert to ensure efficient coupling of catalytic functions, it is suggested that a flexible hinge exists to bring the two sites together for concerted ammonia transfer.
|AA||Uniprot||Uniprot Resid||PDB||PDB Resid|
overall product formed, proton transfer, overall reactant used, unimolecular elimination by the conjugate base, enzyme-substrate complex formation, bimolecular nucleophilic addition, intermediate formation, bimolecular nucleophilic substitution, intermediate terminated, native state of enzyme regenerated, dephosphorylation, deamination, intermediate collapse, enzyme-substrate complex cleavage
The tetrahedral intermediate collapses, liberating ammonia, which deprotonates His181 and then passes to the other catalytic domain. The ammonia produced is transferred from the glutaminase domain to the ATP pyrophosphatase domain. However, the glutaminase and ATP pyrophosphatase domain are approximately 30 Angstroms apart, and it is not yet entirely clear how the liberated ammonia is transported from the glutaminase to the ATP pyrophosphatase domain. It has been suggested that the most likely route is by channelling through the protein in a manner analogous to the classical channelling of common metabolites between sequential enzyme pairs [PMID:9575335]. However, a hinging movement between the two domains has also been suggested [PMID:8548458].
There are no kinetic parameters information for this Enzyme
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