期刊
JOURNAL OF MOLECULAR BIOLOGY
卷 355, 期 5, 页码 980-988出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2005.11.047
关键词
guanosine monophosphate reductase 2; GMP; crystal structure; purine salvage
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 reducatase 2 (hGMPR2) in complex with GMP at 3.0 angstrom 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. (c) 2005 Elsevier Ltd. All rights reserved.
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