3DOY

Crystal structure of (3R)-Hydroxyacyl-Acyl Carrier Protein Dehydratase (FabZ) from Helicobacter pylori in complex with compound 3i

3DOY の概要

• エントリーDOI: 10.2210/pdb3doy/pdb
• 関連するPDBエントリー: 2GLL 3DOZ 3DP0 3DP1 3DP2 3DP3
• 分子名称: (3R)-hydroxymyristoyl-acyl carrier protein dehydratase, CHLORIDE ION, BENZAMIDINE, ... (5 entities in total)
• 機能のキーワード: fabz complex, lyase
• 由来する生物種: Helicobacter pylori (Campylobacter pylori)
• 細胞内の位置: Cytoplasm : Q5G940
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 111067.33

構造登録者

Zhang, L.,He, L.,Liu, X.,Liu, H.,Shen, X.,Jiang, H. (登録日: 2008-07-07, 公開日: 2009-05-05, 最終更新日: 2023-11-01)

主引用文献

He, L.,Zhang, L.,Liu, X.,Li, X.,Zheng, M.,Li, H.,Yu, K.,Chen, K.,Shen, X.,Jiang, H.,Liu, H.
Discovering potent inhibitors against the beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Helicobacter pylori: structure-based design, synthesis, bioassay, and crystal structure determination.
J.Med.Chem., 52:2465-2481, 2009

PubMed Abstract: The discovery of HpFabZ inhibitors is now of special interest in the treatment of various gastric diseases. In this work, three series of derivatives (compounds 3, 4, and 5) were designed, synthesized, and their biological activities were investigated as potential HpFabZ inhibitors in a two phased manner. First, we designed and synthesized two series of derivatives (3a-r and 4a-u) and evaluated the enzyme-based assay against HpFabZ. Five compounds (3i-k, 3m, and 3q) showed potential inhibitory activity, with IC(50) values less than 2 muM. Second, a focused combinatorial library containing 280 molecules was designed employing the LD1.0 program. Twelve compounds (5a-l) were selected and synthesized. The activity of the most potent compound 5h (IC(50) = 0.86 muM) was 46 times higher than that of the hit 1. The high hit rate and the potency of the new HpFabZ inhibitors demonstrated the efficiency of the strategy for the focused library design and virtual screening.

PubMed: 19309082
DOI: 10.1021/jm8015602

実験手法

X-RAY DIFFRACTION (2.4 Å)