The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP.
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Eads JC, Scapin G, Xu Y, Grubmeyer C, Sacchettini JC
The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP.
Cell. 1994 Jul 29;78(2):325-34.
- PubMed ID
- 8044844 [ View in PubMed]
- Abstract
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.