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- Title
The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.
- Authors
Shi, W; Li, C M; Tyler, P C; Furneaux, R H; Grubmeyer, C; Schramm, V L; Almo, S C
- Abstract
The structure of human HGPRT bound to the transition-state analog immucillinGP and Mg2+-pyrophosphate has been determined to 2.0 A resolution. ImmucillinGP was designed as a stable analog with the stereoelectronic features of the transition state. Bound inhibitor at the catalytic site indicates that the oxocarbenium ion of the transition state is stabilized by neighboring-group participation from MgPPi and O5'. A short hydrogen bond forms between Asp 137 and the purine ring analog. Two Mg2+ ions sandwich the pyrophosphate and contact both hydroxyls of the ribosyl analog. The transition-state analog is shielded from bulk solvent by a catalytic loop that moves approximately 25 A to cover the active site and becomes an ordered antiparallel beta-sheet.
- Publication
Nature structural biology, 1999, Vol 6, Issue 6, p588
- ISSN
1072-8368
- Publication type
Journal Article
- DOI
10.1038/9376