4CIX

Crystal structure of Mycobacterium tuberculosis type 2 dehydroquinase in complex with(1R,4R,5R)-1,4,5-trihydroxy-3-((1S)-1-hydroxy-2-phenyl) ethylcyclohex-2-en-1-carboxylic acid

4CIX の概要

• エントリーDOI: 10.2210/pdb4cix/pdb
• 関連するPDBエントリー: 4CIV 4CIW 4CIY
• 分子名称: 3-DEHYDROQUINATE DEHYDRATASE, (1R,4R,5R)-1,4,5-trihydroxy-3-[(1S)-1-hydroxy-2-phenyl]ethylcyclohex-2-ene-1-carboxylic acid, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: bacterial proteins, lyase, inhibitor, protein binding, shikimis acid pathway, substrate specificity
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16163.16

構造登録者

Otero, J.M.,Llamas-Saiz, A.L.,Lamb, H.,Hawkins, A.R.,Blanco, B.,Sedes, A.,Peon, A.,Gonzalez-Bello, C.,van Raaij, M.J. (登録日: 2013-12-17, 公開日: 2014-04-16, 最終更新日: 2023-12-20)

主引用文献

Blanco, B.,Sedes, A.,Peon, A.,Otero, J.M.,van Raaij, M.J.,Thompson, P.,Hawkins, A.R.,Gonzalez-Bello, C.
Exploring the water-binding pocket of the type II dehydroquinase enzyme in the structure-based design of inhibitors.
J. Med. Chem., 57:3494-3510, 2014

PubMed Abstract: Structural and computational studies to explore the WAT1 binding pocket in the structure-based design of inhibitors against the type II dehydroquinase (DHQ2) enzyme are reported. The crystal structures of DHQ2 from M. tuberculosis in complex with four of the reported compounds are described. The electrostatic interaction observed between the guanidinium group of the essential arginine and the carboxylate group of one of the inhibitors in the reported crystal structures supports the recently suggested role of this arginine as the residue that triggers the release of the product from the active site. The results of the structural and molecular dynamics simulation studies revealed that the inhibitory potency is favored by promoting interactions with WAT1 and the residues located within this pocket and, more importantly, by avoiding situations where the ligands occupy the WAT1 binding pocket. The new insights can be used to advantage in the structure-based design of inhibitors.

PubMed: 24689821
DOI: 10.1021/jm500175z

実験手法

X-RAY DIFFRACTION (2.9 Å)