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 journalArticle

17 Citations (Scopus)

Abstract

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
Volume355
Issue number5
DOIs
StatePublished - Feb 3 2006

Fingerprint

GMP Reductase
Inosine Monophosphate
NADP
Catalytic Domain
Purine Nucleosides
Deamination
Sequence Alignment
Coenzymes
NAD
Sequence Analysis
Oxidoreductases
Proteins
human GMPR2 protein
2'-guanylic acid

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP. / Li, Jixi; Wei, Zhiyi; Zheng, Mei; Gu, Xing; Deng, Yingfeng; Qiu, Rui; Chen, Fei; Ji, Chaoneng; Gong, Weimin; Xie, Yi; Mao, Yumin.

In: Journal of Molecular Biology, Vol. 355, No. 5, 03.02.2006, p. 980-988.

Research output: Contribution to journalArticle

Li, J, Wei, Z, Zheng, M, Gu, X, Deng, Y, Qiu, R, Chen, F, Ji, C, Gong, W, Xie, Y & Mao, Y 2006, 'Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP', Journal of Molecular Biology, vol. 355, no. 5, pp. 980-988. https://doi.org/10.1016/j.jmb.2005.11.047
Li, Jixi ; Wei, Zhiyi ; Zheng, Mei ; Gu, Xing ; Deng, Yingfeng ; Qiu, Rui ; Chen, Fei ; Ji, Chaoneng ; Gong, Weimin ; Xie, Yi ; Mao, Yumin. / Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP. In: Journal of Molecular Biology. 2006 ; Vol. 355, No. 5. pp. 980-988.
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