1hmp
From Proteopedia
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THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP
Contents |
Overview
The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 A resolution. The enzyme has a core alpha/beta structure resembling the nucleotide-binding fold of dehydrogenases, and a second lobe composed of residues from the amino and carboxy termini. The GMP molecule binds in an anti conformation in a solvent-exposed cleft of the enzyme. Lys-165, which forms a hydrogen bond to O6 of GMP, appears to be critical for determining the specificity for guanine and hypoxanthine over adenine. The location of active site residues also provides evidence for a possible mechanism for general base-assisted HGPRTase catalysis. A rationalization of the effects on stability and activity of naturally occurring single amino acid mutations of HGPRTase is presented, including a discussion of several mutations at the active site that lead to Lesch-Nyhan syndrome.
Disease
Known diseases associated with this structure: HPRT-related gout OMIM:[308000], Lesch-Nyhan syndrome, 300322, OMIM:[308000]
About this Structure
1HMP is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.
Reference
The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP., Eads JC, Scapin G, Xu Y, Grubmeyer C, Sacchettini JC, Cell. 1994 Jul 29;78(2):325-34. PMID:8044844
Page seeded by OCA on Thu Feb 21 13:02:47 2008
