7CFK

Structure of the CBS domain of the bacterial CNNM/CorC family Mg2+ transporter in complex with the novel inhibitor IGN95a

7CFK の概要

• エントリーDOI: 10.2210/pdb7cfk/pdb
• 分子名称: Hemolysin, (2S)-2-[(6-azanyl-9H-purin-8-yl)sulfanyl]butanoic acid, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• 機能のキーワード: transporter, transport protein
• 由来する生物種: Thermus parvatiensis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41359.54

構造登録者

Huang, Y.,Jin, F.,Hattori, M. (登録日: 2020-06-25, 公開日: 2021-04-21, 最終更新日: 2023-11-29)

主引用文献

Huang, Y.,Mu, K.,Teng, X.,Zhao, Y.,Funato, Y.,Miki, H.,Zhu, W.,Xu, Z.,Hattori, M.
Identification and mechanistic analysis of an inhibitor of the CorC Mg 2+ transporter.
Iscience, 24:102370-102370, 2021

PubMed Abstract: The CorC/CNNM family of Na-dependent Mg transporters is ubiquitously conserved from bacteria to humans. CorC, the bacterial CorC/CNNM family of proteins, is involved in resistance to antibiotic exposure and in the survival of pathogenic microorganisms in their host environment. The CorC/CNNM family proteins possess a cytoplasmic region containing the regulatory ATP-binding site. CorC and CNNM have attracted interest as therapeutic targets, whereas inhibitors targeting the ATP-binding site have not been identified. Here, we performed a virtual screening of CorC by targeting its ATP-binding site, identified a compound named IGN95a with inhibitory effects on ATP binding and Mg export, and determined the cytoplasmic domain structure in complex with IGN95a. Furthermore, a chemical cross-linking experiment indicated that with ATP bound to the cytoplasmic domain, the conformational equilibrium of CorC was shifted more toward the inward-facing state of the transmembrane domain. In contrast, IGN95a did not induce such a shift.

PubMed: 33912817
DOI: 10.1016/j.isci.2021.102370

実験手法

X-RAY DIFFRACTION (2.9 Å)