2a7r

Publication Abstract from PubMed

Guanosine monophosphate reductase (GMPR) catalyzes the irreversible and NADPH-dependent reductive deamination of GMP to IMP, and plays a critical role in re-utilization of free intracellular bases and purine nucleosides. Here, we report the first crystal structure of human GMP reductase 2 (hGMPR2) in complex with GMP at 3.0 A resolution. The protein forms a tetramer composed of subunits adopting the ubiquitous (alpha/beta)8 barrel fold. Interestingly, the substrate GMP is bound to hGMPR2 through interactions with Met269, Ser270, Arg286, Ser288, and Gly290; this makes the conformation of the adjacent flexible binding region (residues 268-289) fixed, much like a door on a hinge. Structure comparison and sequence alignment analyses show that the conformation of the active site loop (residues 179-187) is similar to those of hGMPR1 and inosine monophosphate dehydrogenases (IMPDHs). We propose that Cys186 is the potential active site, and that the conformation of the loop (residues 129-133) suggests a preference for the coenzyme NADPH over NADH. This structure provides important information towards understanding the functions of members of the GMPR family.

Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP.,Li J, Wei Z, Zheng M, Gu X, Deng Y, Qiu R, Chen F, Ji C, Gong W, Xie Y, Mao Y J Mol Biol. 2006 Feb 3;355(5):980-8. Epub 2005 Dec 1. PMID:16359702^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.