4CNO

Structure of the Salmonella typhi Type I dehydroquinase inhibited by a 3-dehydroquinic acid derivative

4CNO の概要

• エントリーDOI: 10.2210/pdb4cno/pdb
• 関連するPDBエントリー: 4CNN 4CNP
• 分子名称: 3-DEHYDROQUINATE DEHYDRATASE, (2R)-2-METHYL-3-DEHYDROQUINIC ACID (3 entities in total)
• 機能のキーワード: lyase, inhibitor, protein binding, shikimis acid pathway, substrate specificity
• 由来する生物種: SALMONELLA ENTERICA SUBSP. ENTERICA SEROVAR TYPHI
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 111540.68

構造登録者

Otero, J.M.,Llamas-Saiz, A.L.,Maneiro, M.,Peon, A.,Lence, E.,Lamb, H.,Hawkins, A.R.,Gonzalez-Bello, C.,van Raaij, M.J. (登録日: 2014-01-23, 公開日: 2014-10-08, 最終更新日: 2023-12-20)

主引用文献

Maneiro, M.,Peon, A.,Lence, E.,Otero, J.M.,Van Raaij, M.J.,Thompson, P.,Hawkins, A.R.,Gonzalez-Bello, C.
Insights into substrate binding and catalysis in bacterial type I dehydroquinase.
Biochem. J., 462:415-424, 2014

PubMed Abstract: Structural, biochemical and computational studies to study substrate binding and the role of the conserved residues of the DHQ1 (type I dehydroquinase) enzyme active site are reported in the present paper. The crystal structure of DHQ1 from Salmonella typhi in complex with (2R)-2-methyl-3-dehydroquinic acid, a substrate analogue, was solved at 1.5 Å. The present study reveals a previously unknown key role for conserved Glu46, Phe145 and Met205 and Gln236, Pro234 and Ala233 residues, with the latter three being located in the flexible substrate-covering loop. Gln236 was shown to be responsible for the folding of this loop and for the dramatic reduction of its flexibility, which triggers active site closure. Glu46 was found to be key in bringing the substrate close to the lysine/histidine catalytic pocket to initiate catalysis. The present study could be useful in the rational design of inhibitors of this challenging and recognized target for the development of novel herbicides and antimicrobial agents.

PubMed: 24957267
DOI: 10.1042/BJ20140614

実験手法

X-RAY DIFFRACTION (1.5 Å)