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| THE CRYSTAL-STRUCTURE OF HUMAN HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE WITH BOUND GMP |
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| Author(s): EADS JC, SCAPIN G, XU YM, GRUBMEYER C, SACCHETTINI JC |
| Source: CELL Volume: 78 Issue: 2 Pages: 325-334 Published: JUL 29 1994 |
| Times Cited: 160 References: 47 |
| Abstract: The crystal structure of HGPRTase with bound GMP has been determined and refined to 2.5 Angstrom 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: EADS, JC (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED, DEPT BIOCHEM, 1300 MORRIS PK AVE, BRONX, NY 10461 USA |
Addresses:
1. TEMPLE UNIV, SCH MED, DEPT BIOCHEM, PHILADELPHIA, PA 19140 USA
2. FELS INST CANC RES, PHILADELPHIA, PA 19140 USA |
| Publisher: CELL PRESS, 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: NZ242 |
| ISSN: 0092-8674 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |