Guanosine monophosphate synthase (GMPS)

Guanosine monophosphate synthase (GMPS) is a protein-coding enzyme that catalyzes the conversion of xanthosine monophosphate (XMP) to guanosine monophosphate (GMP) in the presence of glutamine and ATP, forming a key step in purine nucleotide biosynthesis. GMPS is a member of the glutamine amidotransferase family, featuring two catalytic domains: a glutaminase domain for glutamine hydrolysis, and an ATP pyrophosphatase domain for the formation and subsequent amination of the adenyl-XMP intermediate. GMPS plays vital roles in DNA replication and cell proliferation, and its dysregulation, upregulation, or altered activity is linked to cancer progression and other proliferative disorders. Its essential role in pathogenic organisms also makes it a molecular target for anticancer and antiprotozoal drug development. Allosteric regulation, ammonia channeling, and domain crosstalk are key molecular features that influence its enzymatic activity and may provide avenues for selective inhibition.

Other names

GMP synthaseGMP synthetaseGuanine monophosphate synthetaseGuanine monophosphate synthaseGlutamine amidotransferaseGATD7GMP synthase [glutamine-hydrolyzing]Guanosine 5'-monophosphate synthaseTesticular tissue protein Li 82MLL/GMPS fusion protein

Inhibition of enzymatic activity: Small molecules inhibit GMPS by blocking ammonia channeling, allosteric activation, or domain interactions. Inhibitors may target the enzyme's active sites (glutaminase domain, ATP pyrophosphatase domain) or interfere with dimerization/allostery.