3DP1

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

Summary for 3DP1

• Entry DOI: 10.2210/pdb3dp1/pdb
• Related: 2GLL 3DOY 3DOZ 3DP0 3DP2 3DP3
• Descriptor: (3R)-hydroxymyristoyl-acyl carrier protein dehydratase, CHLORIDE ION, BENZAMIDINE, ... (5 entities in total)
• Functional Keywords: fabz complex, lyase
• Biological source: Helicobacter pylori (Campylobacter pylori)
• Cellular location: Cytoplasm (By similarity): Q5G940
• Total number of polymer chains: 6
• Total formula weight: 110938.34

Authors

Zhang, L.,He, L.,Liu, X.,Liu, H.,Shen, X.,Jiang, H. (deposition date: 2008-07-07, release date: 2009-05-05, Last modification date: 2023-11-01)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)