1hmp
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| , resolution 2.5Å | |||||||
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| Ligands: | |||||||
| Activity: | Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: HPRT-related gout OMIM:[308000], Lesch-Nyhan syndrome, 300322, OMIM:[308000]
About this StructureAbout this Structure
1HMP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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