7cfk

Publication Abstract from PubMed

The CorC/CNNM family of Na(+)-dependent Mg(2+) 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(2+) 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.

Identification and mechanistic analysis of an inhibitor of the CorC Mg(2+) transporter.,Huang Y, Mu K, Teng X, Zhao Y, Funato Y, Miki H, Zhu W, Xu Z, Hattori M iScience. 2021 Mar 26;24(4):102370. doi: 10.1016/j.isci.2021.102370. eCollection , 2021 Apr 23. PMID:33912817^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.