1BZY

HUMAN HGPRTASE WITH TRANSITION STATE INHIBITOR

1BZY の概要

• エントリーDOI: 10.2210/pdb1bzy/pdb
• 分子名称: HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE, MAGNESIUM ION, PHOSPHORIC ACID MONO-[5-(2-AMINO-4-OXO-4,5-DIHYDRO-3H-PYRROLO[3,2-D]PYRIMIDIN-7-YL)-3,4-DIHYDROXY-PYRROLIDIN-2-YLMETHYL] ESTER, ... (5 entities in total)
• 機能のキーワード: phosphoribosyltransferase, immucillin, lesch-nyhan, hgprt, transition state, magnesium, pyrophosphate, oxocarbenium ion, neighboring group participation
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P00492
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 100268.14

構造登録者

Shi, W.,Li, C.,Tyler, P.C.,Furneaux, R.H.,Grubmeyer, C.,Schramm, V.L.,Almo, S.C. (登録日: 1998-11-05, 公開日: 1999-06-22, 最終更新日: 2024-05-22)

主引用文献

Shi, W.,Li, C.M.,Tyler, P.C.,Furneaux, R.H.,Grubmeyer, C.,Schramm, V.L.,Almo, S.C.
The 2.0 A structure of human hypoxanthine-guanine phosphoribosyltransferase in complex with a transition-state analog inhibitor.
Nat.Struct.Biol., 6:588-593, 1999

PubMed 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.

PubMed: 10360366
DOI: 10.1038/9376

実験手法

X-RAY DIFFRACTION (2 Å)