9wxs

Silver-bound E.coli Malate dehydrogenase (C251S)

spinqualitylabelsall models 9wxs, resolution 1.56Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9wxs is a 4 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.56Å Ligands: AG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function MDH_ECOLI Catalyzes the reversible oxidation of malate to oxaloacetate.[HAMAP-Rule:MF_01516] Publication Abstract from PubMed Metal ions may functionally inhibit metalloproteins via either replacement of intact metal cofactors or binding to allosteric sites via metalloallostery. Despite extensive studies, until now, it has not been fully understood how silver inhibits its authentic protein targets, particularly at the atomic level, largely owing to the lack of knowledge on the authentic protein targets of silver as well as the limited structures available. Herein we show that malate dehydrogenase (MDH) serves as a vital target of antimicrobial Ag(+) against E. coli. Ag(+) binds MDH at multiple sites and inhibits its activity via a non-competitive mechanism. Importantly, we successfully captured the Ag(+)-mediated "open-to-closed" conformational change of the active-site of MDH by X-ray crystallography. Combined with the enzyme kinetics and mutagenesis data, we unambiguously unveil that the allosteric inhibition of MDH by Ag(+) is attributable to its binding to the cysteine residue (Cys251), consequently leading to the closure of the active-site loop of MDH, which disrupts the substrate and coenzyme binding, and ultimately inhibiting the activity of MDH. Our studies provide the first structural glimpse of an unprecedented allosteric inhibition of authentic target enzymes by silver. These findings not only enhance our understanding of the mechanism underlying silver inhibition of its protein targets at the atomic level, but also offer a novel allosteric targeting site in MDH for the design of new antibiotics. Unprecedented allosteric inhibition of E. coli malate dehydrogenase by silver(i) from atomic resolution analysis.,Wang H, Wang M, Yang X, Yan A, Hao Q, Li H, Sun H Chem Sci. 2025 Sep 19. doi: 10.1039/d5sc05183e. PMID:41104151 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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