| Structural highlights
Function
GMPR2_HUMAN Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides. Plays a role in modulating cellular differentiation.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deng Y, Wang Z, Ying K, Gu S, Ji C, Huang Y, Gu X, Wang Y, Xu Y, Li Y, Xie Y, Mao Y. NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties. Int J Biochem Cell Biol. 2002 Sep;34(9):1035-50. PMID:12009299
- ↑ Zhang J, Zhang W, Zou D, Chen G, Wan T, Zhang M, Cao X. Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells. J Cancer Res Clin Oncol. 2003 Feb;129(2):76-83. Epub 2003 Mar 1. PMID:12669231 doi:http://dx.doi.org/10.1007/s00432-002-0413-7
- ↑ Li J, Wei Z, Zheng M, Gu X, Deng Y, Qiu R, Chen F, Ji C, Gong W, Xie Y, Mao Y. Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP. J Mol Biol. 2006 Feb 3;355(5):980-8. Epub 2005 Dec 1. PMID:16359702 doi:10.1016/j.jmb.2005.11.047
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