3N2E

Crystal structure of Helicobactor pylori shikimate kinase in complex with NSC162535

3N2E の概要

• エントリーDOI: 10.2210/pdb3n2e/pdb
• 関連するPDBエントリー: 1ZUH 1ZUI 3HR7 3MRS 3MUF
• 分子名称: Shikimate kinase, 7-amino-4-hydroxy-3-[(E)-(5-hydroxy-7-sulfonaphthalen-2-yl)diazenyl]naphthalene-2-sulfonic acid, L(+)-TARTARIC ACID, ... (4 entities in total)
• 機能のキーワード: alpha-beta-alpha fold, transferase
• 由来する生物種: Helicobacter pylori
• 細胞内の位置: Cytoplasm (Probable): P56073
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 58741.80

構造登録者

Cheng, W.C.,Chen, T.J.,Lin, S.C.,Wang, W.C. (登録日: 2010-05-18, 公開日: 2011-05-18, 最終更新日: 2023-11-01)

主引用文献

Cheng, W.C.,Chen, Y.F.,Wang, H.J.,Hsu, K.C.,Lin, S.C.,Chen, T.J.,Yang, J.M.,Wang, W.C.
Structures of Helicobacter pylori shikimate kinase reveal a selective inhibitor-induced-fit mechanism
Plos One, 7:e33481-e33481, 2012

PubMed Abstract: Shikimate kinase (SK), which catalyzes the specific phosphorylation of the 3-hydroxyl group of shikimic acid in the presence of ATP, is the enzyme in the fifth step of the shikimate pathway for biosynthesis of aromatic amino acids. This pathway is present in bacteria, fungi, and plants but absent in mammals and therefore represents an attractive target pathway for the development of new antimicrobial agents, herbicides, and antiparasitic agents. Here we investigated the detailed structure-activity relationship of SK from Helicobacter pylori (HpSK). Site-directed mutagenesis and isothermal titration calorimetry studies revealed critical conserved residues (D33, F48, R57, R116, and R132) that interact with shikimate and are therefore involved in catalysis. Crystal structures of HpSK·SO(4), R57A, and HpSK•shikimate-3-phosphate • ADP show a characteristic three-layer architecture and a conformationally elastic region consisting of F48, R57, R116, and R132, occupied by shikimate. The structure of the inhibitor complex, E114A • 162535, was also determined, which revealed a dramatic shift in the elastic LID region and resulted in conformational locking into a distinctive form. These results reveal considerable insight into the active-site chemistry of SKs and a selective inhibitor-induced-fit mechanism.

PubMed: 22438938
DOI: 10.1371/journal.pone.0033481

実験手法

X-RAY DIFFRACTION (2.53 Å)