1grv

From Proteopedia

Revision as of 14:12, 5 November 2007

HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE FROM E. COLI

Overview

Crystal structures have been determined for free Escherichia coli, hypoxanthine phosphoribosyltransferase (HPRT) (2.9 A resolution) and for, the enzyme in complex with the reaction products, inosine 5'-monophosphate, (IMP) and guanosine 5'-monophosphate (GMP) (2.8 A resolution). Of the, known 6-oxopurine phosphoribosyltransferase (PRTase) structures, E. coli, HPRT is most similar in structure to that of Tritrichomonas foetus HGXPRT, with a rmsd for 150 Calpha atoms of 1.0 A. Comparison of the free and, product bound structures shows that the side chain of Phe156 and the, polypeptide backbone in this vicinity move to bind IMP or GMP. A, nonproline cis peptide bond, also found in some other 6-oxopurine PRTases, is observed between Leu46 and Arg47 in both the free and complexed, structures. For catalysis to occur, the 6-oxopurine PRTases have a, requirement for divalent metal ion, usually Mg(2+) in vivo. In the free, structure, a Mg(2+) is coordinated to the side chains of Glu103 and, Asp104. This interaction may be important for stabilization of the enzyme, before catalysis. E. coli HPRT is unique among the known 6-oxopurine, PRTases in that it exhibits a marked preference for hypoxanthine as, substrate over both xanthine and guanine. The structures suggest that its, substrate specificity is due to the modes of binding of the bases. In E., coli HPRT, the carbonyl oxygen of Asp163 would likely form a hydrogen bond, with the 2-exocyclic nitrogen of guanine (in the, HPRT-guanine-PRib-PP-Mg(2+) complex). However, hypoxanthine does not have, a 2-exocyclic atom and the HPRT-IMP structure suggests that hypoxanthine, is likely to occupy a different position in the purine-binding pocket.

About this Structure

1GRV is a Single protein structure of sequence from Escherichia coli with MG as ligand. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Structure known Active Site: MGA. Full crystallographic information is available from OCA.

Reference

Crystal structures of free, IMP-, and GMP-bound Escherichia coli hypoxanthine phosphoribosyltransferase., Guddat LW, Vos S, Martin JL, Keough DT, de Jersey J, Protein Sci. 2002 Jul;11(7):1626-38. PMID:12070315

Page seeded by OCA on Mon Nov 5 16:17:57 2007