6GJV

apo-structure of IMPDH from Pseudomonas aeruginosa

6GJV の概要

• エントリーDOI: 10.2210/pdb6gjv/pdb
• 分子名称: Inosine-5'-monophosphate dehydrogenase (2 entities in total)
• 機能のキーワード: inosine-5'-monophosphate dehydrogenase, oxidoreductase
• 由来する生物種: Pseudomonas aeruginosa PAO1
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 431509.59

構造登録者

Labesse, G.,Haouz, A.,Alexandre, T.,Munier-Lehmann, H. (登録日: 2018-05-17, 公開日: 2019-02-27, 最終更新日: 2024-01-17)

主引用文献

Alexandre, T.,Lupan, A.,Helynck, O.,Vichier-Guerre, S.,Dugue, L.,Gelin, M.,Haouz, A.,Labesse, G.,Munier-Lehmann, H.
First-in-class allosteric inhibitors of bacterial IMPDHs.
Eur J Med Chem, 167:124-132, 2019

PubMed Abstract: Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme in many bacterial pathogens and is considered as a potential drug target for the development of new antibacterial agents. Our recent work has revealed the crucial role of one of the two structural domains (i.e. Bateman domain) in the regulation of the quaternary structure and enzymatic activity of bacterial IMPDHs. Thus, we have screened chemical libraries to search for compounds targeting the Bateman domain and identified first in-class allosteric inhibitors of a bacterial IMPDH. These inhibitors were shown to counteract the activation by the natural positive effector, MgATP, and to block the enzyme in its apo conformation (low affinity for IMP). Our structural studies demonstrate the versatility of the Bateman domain to accommodate totally unrelated chemical scaffolds and pave the way for the development of allosteric inhibitors, an avenue little explored until now.

PubMed: 30769241
DOI: 10.1016/j.ejmech.2019.01.064

実験手法

X-RAY DIFFRACTION (2.11 Å)