3N9S

Class II fructose-1,6-bisphosphate aldolase from helicobacter pylori in complex with N-(4-hydroxybutyl)- glycolohydroxamic acid bis-phosphate, a competitive inhibitor

3N9S の概要

• エントリーDOI: 10.2210/pdb3n9s/pdb
• 関連するPDBエントリー: 3C4U 3C52 3C56 3N9R
• 分子名称: Fructose-bisphosphate aldolase, 4-{hydroxy[(phosphonooxy)acetyl]amino}butyl dihydrogen phosphate, ZINC ION, ... (6 entities in total)
• 機能のキーワード: fbp aldolase, class ii, inhibitor, lyase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• 由来する生物種: Helicobacter pylori
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68504.84

構造登録者

Coincon, M.,Sygusch, S. (登録日: 2010-05-31, 公開日: 2010-11-17, 最終更新日: 2023-09-06)

主引用文献

Daher, R.,Fonvielle, M.,Gest, P.M.,Guerin, M.E.,Jackson, M.,Sygusch, J.,Therisod, M.
Rational Design, Synthesis, and Evaluation of New Selective Inhibitors of Microbial Class II (Zinc Dependent) Fructose Bis-phosphate Aldolases.
J.Med.Chem., 53:7836-7842, 2010

PubMed Abstract: We report the synthesis and biochemical evaluation of several selective inhibitors of class II (zinc dependent) fructose bis-phosphate aldolases (Fba). The products were designed as transition-state analogues of the catalyzed reaction, structurally related to the substrate fructose bis-phosphate (or sedoheptulose bis-phosphate) and based on an N-substituted hydroxamic acid, as a chelator of the zinc ion present in active site. The compounds synthesized were tested on class II Fbas from various pathogenic microorganisms and, by comparison, on a mammalian class I Fba. The best inhibitor shows K(i) against class II Fbas from various pathogens in the nM range, with very high selectivity (up to 10(5)). Structural analyses of inhibitors in complex with aldolases rationalize and corroborate the enzymatic kinetics results. These inhibitors represent lead compounds for the preparation of new synthetic antibiotics, notably for tuberculosis prophylaxis.

PubMed: 20929256
DOI: 10.1021/jm1009814

実験手法

X-RAY DIFFRACTION (1.85 Å)