3CLH

Crystal structure of 3-dehydroquinate synthase (DHQS)from Helicobacter pylori

3CLH の概要

• エントリーDOI: 10.2210/pdb3clh/pdb
• 分子名称: 3-dehydroquinate synthase, ZINC ION, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (4 entities in total)
• 機能のキーワード: shikimate pathway, aromatic amino acid biosynthesis, dhqs, amino-acid biosynthesis, cytoplasm, lyase, nad
• 由来する生物種: Helicobacter pylori (Campylobacter pylori)
• 細胞内の位置: Cytoplasm (Probable): P56081
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 79809.30

構造登録者

Wang, W.C.,Liu, J.S.,Cheng, W.C.,Wang, H.J.,Chen, Y.C. (登録日: 2008-03-19, 公開日: 2009-03-24, 最終更新日: 2023-11-01)

主引用文献

Liu, J.S.,Cheng, W.C.,Wang, H.J.,Chen, Y.C.,Wang, W.C.
Structure-based inhibitor discovery of Helicobacter pylori dehydroquinate synthase.
Biochem.Biophys.Res.Commun., 373:1-7, 2008

PubMed Abstract: Dehydroquinate synthase (DHQS) is a nicotinamide adenine dinucleotide (NAD)-dependent enzyme that converts 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAHP) into 3-dehydroquinate (DHQ). Since it catalyzes the second key step in the shikimate pathway, which is crucial for the aromatic amino acid metabolism in bacteria, fungi, and plants, but not in mammals, DHQS is a potential target for new antimicrobial agents, anti-parasitic agents and herbicides. The crystal structure of Helicobacter pylori DHQS (HpDHQS) complexed with NAD has been determined at 2.4-A resolution and was found to possess an N-terminal Rossmann-fold domain and a C-terminal alpha-helical domain. Structural comparison reveals that the binary complex adopts an open-state conformation and shares conserved residues in the binding pocket. Virtual docking of compounds into the active site of the HpDHQS structure using the GOLD docking program led to the identification of several inhibitors. The most active compound had an IC(50) value of 61 microM, which may serve as a lead for potent inhibitors.

PubMed: 18503755
DOI: 10.1016/j.bbrc.2008.05.070

実験手法

X-RAY DIFFRACTION (2.4 Å)