2PU1

Crystal Structure of the T. brucei enolase complexed with Fluoro-phosphonoacetohydroxamate (FPAH)

2PU1 の概要

• エントリーDOI: 10.2210/pdb2pu1/pdb
• 関連するPDBエントリー: 1oep 2ptw 2ptx 2pty 2ptz 2pu0
• 分子名称: Enolase, ZINC ION, [(1S)-1-FLUORO-2-(HYDROXYAMINO)-2-OXOETHYL]PHOSPHONIC ACID, ... (5 entities in total)
• 機能のキーワード: lyase, glycolysis, his-tag
• 由来する生物種: Trypanosoma brucei
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 47335.77

構造登録者

Navarro, M.V.A.S.,Rigden, D.J.,Garratt, R.C.,Dias, S.M.G. (登録日: 2007-05-08, 公開日: 2007-11-20, 最終更新日: 2023-08-30)

主引用文献

Navarro, M.V.,Gomes Dias, S.M.,Mello, L.V.,da Silva Giotto, M.T.,Gavalda, S.,Blonski, C.,Garratt, R.C.,Rigden, D.J.
Structural flexibility in Trypanosoma brucei enolase revealed by X-ray crystallography and molecular dynamics.
Febs J., 274:5077-5089, 2007

PubMed Abstract: Enolase is a validated drug target in Trypanosoma brucei. To better characterize its properties and guide drug design efforts, we have determined six new crystal structures of the enzyme, in various ligation states and conformations, and have carried out complementary molecular dynamics simulations. The results show a striking structural diversity of loops near the catalytic site, for which variation can be interpreted as distinct modes of conformational variability that are explored during the molecular dynamics simulations. Our results show that sulfate may, unexpectedly, induce full closure of catalytic site loops whereas, conversely, binding of inhibitor phosphonoacetohydroxamate may leave open a tunnel from the catalytic site to protein surface offering possibilities for drug development. We also present the first complex of enolase with a novel inhibitor 2-fluoro-2-phosphonoacetohydroxamate. The molecular dynamics results further encourage efforts to design irreversible species-specific inhibitors: they reveal that a parasite enzyme-specific lysine may approach the catalytic site more closely than crystal structures suggest and also cast light on the issue of accessibility of parasite enzyme-specific cysteines to chemically modifying reagents. One of the new sulfate structures contains a novel metal-binding site IV within the catalytic site cleft.

PubMed: 17822439
DOI: 10.1111/j.1742-4658.2007.06027.x

実験手法

X-RAY DIFFRACTION (1.8 Å)