摘要：SummaryThe CorC/CNNM family of Na+-dependent Mg2+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 Mg2+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.Graphical abstractDisplay OmittedHighlights•A compound, IGN95a, inhibited ATP binding and Mg2+export of the CorC Mg2+transporter•The CorC cytoplasmic domain structure in complex with IGN95a was determined•ATP shifted the CorC conformational equilibrium toward the inward-facing state•In contrast, IGN95a binding did not induce such a shiftChemical Compound ; Membranes ; Structural Biology
