1HMP

THE CRYSTAL STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP

Summary for 1HMP

• Entry DOI: 10.2210/pdb1hmp/pdb
• Descriptor: HYPOXANTHINE GUANINE PHOSPHORIBOSYL-TRANSFERASE, GUANOSINE-5'-MONOPHOSPHATE (3 entities in total)
• Functional Keywords: transferase (glycosyltransferase)
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 49688.88

Authors

Eads, J.C.,Scapin, G.,Xu, Y.,Grubmeyer, C.,Sacchettini, J.C. (deposition date: 1994-06-03, release date: 1995-06-03, Last modification date: 2024-02-07)

Primary citation

Eads, J.C.,Scapin, G.,Xu, Y.,Grubmeyer, C.,Sacchettini, J.C.
The crystal structure of human hypoxanthine-guanine phosphoribosyltransferase with bound GMP.
Cell(Cambridge,Mass.), 78:325-334, 1994

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.

PubMed: 8044844
DOI: 10.1016/0092-8674(94)90301-8

Experimental method

X-RAY DIFFRACTION (2.5 Å)