2WKS

Structure of Helicobacter pylori Type II Dehydroquinase with a new carbasugar-thiophene inhibitor.

2WKS の概要

• エントリーDOI: 10.2210/pdb2wks/pdb
• 関連するPDBエントリー: 1J2Y 2C4V 2C4W 2C57
• 分子名称: 3-DEHYDROQUINATE DEHYDRATASE, (1R,4S,5R)-1,4,5-trihydroxy-3-[(5-methyl-1-benzothiophen-2-yl)methoxy]cyclohex-2-ene-1-carboxylic acid (3 entities in total)
• 機能のキーワード: aromatic amino acid biosynthesis, lyase, shikimic acid pathway, 3-dehydroquinate dehydratase
• 由来する生物種: HELICOBACTER PYLORI
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 113097.79

構造登録者

Otero, J.M.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,Prazeres, V.F.V.,Tizon, L.,Castedo, L.,Lamb, H.,Hawkins, A.R.,Gonzalez-Bello, C.,van Raaij, M.J. (登録日: 2009-06-17, 公開日: 2009-11-24, 最終更新日: 2023-12-13)

主引用文献

Prazeres, V.F.,Tizon, L.,Otero, J.M.,Guardado-Calvo, P.,Llamas-Saiz, A.L.,van Raaij, M.J.,Castedo, L.,Lamb, H.,Hawkins, A.R.,Gonzalez-Bello, C.
Synthesis and biological evaluation of new nanomolar competitive inhibitors of Helicobacter pylori type II dehydroquinase. Structural details of the role of the aromatic moieties with essential residues.
J. Med. Chem., 53:191-200, 2010

PubMed Abstract: The shikimic acid pathway is essential to many pathogens but absent in mammals. Enzymes in its pathway are therefore appropriate targets for the development of novel antibiotics. Dehydroquinase is the third enzyme of the pathway, catalyzing the reversible dehydratation of 3-dehydroquinic acid to form 3-dehydroshikimic acid. Here we present the synthesis of novel inhibitors with high affinity for Helicobacter pylori type II dehydroquinase and efficient inhibition characteristics. The structure of Helicobacter pylori type II dehydroquinase in complex with the most potent inhibitor shows that the aromatic functional group interacts with the catalytic Tyr22 by pi-stacking, expelling the Arg17 side chain, which is essential for catalysis, from the active site. The structure therefore explains the favorable properties of the inhibitor and will aid in design of improved antibiotics.

PubMed: 19911771
DOI: 10.1021/jm9010466

実験手法

X-RAY DIFFRACTION (2.95 Å)