The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP
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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.
author list (cited authors)
Eads, J. C., Scapin, G., Xu, Y., Grubmeyer, C., & Sacchettini, J. C.
complete list of authors
Eads, JC||Scapin, G||Xu, Y||Grubmeyer, C||Sacchettini, JC