1fsg

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spinqualitylabelsall models 1fsg, resolution 1.05Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

TOXOPLASMA GONDII HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE COMPLEXED WITH 9-DEAZAGUANINE, ALPHA-D-5-PHOSPHORIBOSYL-1-PYROPHOSPHATE (PRPP) AND TWO MG2+ IONS

Overview

BACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are, well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic, representative of the phosphoribosyltransferase family of enzymes, which, includes other important biosynthetic and salvage enzymes and drug, targets. To better understand the reaction mechanism of this enzyme, we, have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii, as a ternary complex with a substrate and a substrate analog. RESULTS: The, crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a, nonreactive substrate analog, 9-deazaguanine, bound in the active site has, been determined at 1.05 A resolution and refined to a free R factor of, 15.4%. This structure constitutes the first atomic-resolution structure of, both a phosphoribosyltransferase and the central metabolic substrate PRPP., This pre-transition state complex provides a clearer understanding of the, structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of, substrate deformation, chief among them an unexpected C2'-endo pucker, adopted by the PRPP ribose ring, raise the energy of the ground state. A, cation-pi interaction between Tyr-118 and the developing oxocarbenium ion, in the ribose ring helps to stabilize the transition state. Enforced, substrate propinquity coupled with optimal reactive geometry for both the, substrates and the active site residues with which they interact, contributes to catalysis as well.

About this Structure

1FSG is a Single protein structure of sequence from Toxoplasma gondii with MG, PRP and 9DG as ligands. Active as Hypoxanthine phosphoribosyltransferase, with EC number 2.4.2.8 Full crystallographic information is available from OCA.

Reference

Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis., Heroux A, White EL, Ross LJ, Kuzin AP, Borhani DW, Structure. 2000 Dec 15;8(12):1309-18. PMID:11188695

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