3ZGN

Crystal structures of Escherichia coli IspH in complex with TMBPP a potent inhibitor of the methylerythritol phosphate pathway

3ZGN の概要

• エントリーDOI: 10.2210/pdb3zgn/pdb
• 関連するPDBエントリー: 3ZGL
• 分子名称: 4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE, (2E)-3-methyl-4-sulfanylbut-2-en-1-yl trihydrogen diphosphate, IRON/SULFUR CLUSTER, ... (4 entities in total)
• 機能のキーワード: oxidoreductase, mep pathway, inhibitors, 4fe-4s cluster
• 由来する生物種: ESCHERICHIA COLI
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 74538.63

構造登録者

Borel, F.,Barbier, E.,Kratsutsky, S.,Janthawornpong, K.,Rohmer, M.,Dale Poulter, C.,Ferrer, J.L.,Seemann, M. (登録日: 2012-12-18, 公開日: 2013-01-09, 最終更新日: 2023-12-20)

主引用文献

Borel, F.,Barbier, E.,Krasutsky, S.,Janthawornpong, K.,Chaignon, P.,Poulter, C.D.,Ferrer, J.L.,Seemann, M.
Further Insight into Crystal Structures of Escherichia coli IspH/LytB in Complex with Two Potent Inhibitors of the MEP Pathway: A Starting Point for Rational Design of New Antimicrobials.
Chembiochem, 18:2137-2144, 2017

PubMed Abstract: IspH, also called LytB, a protein involved in the biosynthesis of isoprenoids through the methylerythritol phosphate pathway, is an attractive target for the development of new antimicrobial drugs. Here, we report crystal structures of Escherichia coli IspH in complex with the two most potent inhibitors: (E)-4-mercapto-3-methylbut-2-en-1-yl diphosphate (TMBPP) and (E)-4-amino-3-methylbut-2-en-1-yl diphosphate (AMBPP) at 1.95 and 1.7 Å resolution, respectively. The structure of the E. coli IspH:TMBPP complex exhibited two conformers of the inhibitor. This unexpected feature was exploited to design and evolve new antimicrobial candidates in silico.

PubMed: 28862365
DOI: 10.1002/cbic.201700363

実験手法

X-RAY DIFFRACTION (1.95 Å)