7CFK

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

Summary for 7CFK

• Entry DOI: 10.2210/pdb7cfk/pdb
• Descriptor: Hemolysin, (2S)-2-[(6-azanyl-9H-purin-8-yl)sulfanyl]butanoic acid, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: transporter, transport protein
• Biological source: Thermus parvatiensis
• Total number of polymer chains: 2
• Total formula weight: 41359.54

Authors

Huang, Y.,Jin, F.,Hattori, M. (deposition date: 2020-06-25, release date: 2021-04-21, Last modification date: 2023-11-29)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.9 Å)