Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP

Jixi Li, Zhiyi Wei, Mei Zheng, Xing Gu, Yingfeng Deng, Rui Qiu, Fei Chen, Chaoneng Ji, Weimin Gong, Yi Xie, Yumin Mao

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


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 Å resolution. The protein forms a tetramer composed of subunits adopting the ubiquitous (α/β)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.

Original languageEnglish (US)
Pages (from-to)980-988
Number of pages9
JournalJournal of Molecular Biology
Issue number5
StatePublished - Feb 3 2006


  • Crystal structure
  • GMP
  • Guanosine monophosphate reductase 2
  • Purine salvage

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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