3M7W

Crystal Structure of Type I 3-Dehydroquinate Dehydratase (aroD) from Salmonella typhimurium LT2 in Covalent Complex with Dehydroquinate

3M7W の概要

• エントリーDOI: 10.2210/pdb3m7w/pdb
• 関連するPDBエントリー: 3L2I 3LB0
• 分子名称: 3-dehydroquinate dehydratase, 1,3,4-TRIHYDROXY-5-OXO-CYCLOHEXANECARBOXYLIC ACID, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: type i 3-dehydroquinase, dhqase_i, dehydroquinate, idp90922, amino-acid biosynthesis, aromatic amino acid biosynthesis, lyase, schiff base, center for structural genomics of infectious diseases, csgid
• 由来する生物種: Salmonella enterica subsp. enterica serovar Typhimurium
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 168208.13

構造登録者

Minasov, G.,Light, S.H.,Shuvalova, L.,Papazisi, L.,Anderson, W.F.,Center for Structural Genomics of Infectious Diseases (CSGID) (登録日: 2010-03-17, 公開日: 2010-04-07, 最終更新日: 2024-11-27)

主引用文献

Light, S.H.,Minasov, G.,Shuvalova, L.,Duban, M.E.,Caffrey, M.,Anderson, W.F.,Lavie, A.
Insights into the mechanism of type I dehydroquinate dehydratases from structures of reaction intermediates.
J.Biol.Chem., 286:3531-3539, 2011

PubMed Abstract: The biosynthetic shikimate pathway consists of seven enzymes that catalyze sequential reactions to generate chorismate, a critical branch point in the synthesis of the aromatic amino acids. The third enzyme in the pathway, dehydroquinate dehydratase (DHQD), catalyzes the dehydration of 3-dehydroquinate to 3-dehydroshikimate. We present three crystal structures of the type I DHQD from the intestinal pathogens Clostridium difficile and Salmonella enterica. Structures of the enzyme with substrate and covalent pre- and post-dehydration reaction intermediates provide snapshots of successive steps along the type I DHQD-catalyzed reaction coordinate. These structures reveal that the position of the substrate within the active site does not appreciably change upon Schiff base formation. The intermediate state structures reveal a reaction state-dependent behavior of His-143 in which the residue adopts a conformation proximal to the site of catalytic dehydration only when the leaving group is present. We speculate that His-143 is likely to assume differing catalytic roles in each of its observed conformations. One conformation of His-143 positions the residue for the formation/hydrolysis of the covalent Schiff base intermediates, whereas the other conformation positions the residue for a role in the catalytic dehydration event. The fact that the shikimate pathway is absent from humans makes the enzymes of the pathway potential targets for the development of non-toxic antimicrobials. The structures and mechanistic insight presented here may inform the design of type I DHQD enzyme inhibitors.

PubMed: 21087925
DOI: 10.1074/jbc.M110.192831

実験手法

X-RAY DIFFRACTION (1.95 Å)