View source for 9wxs


==Silver-bound E.coli Malate dehydrogenase (C251S)==
<StructureSection load='9wxs' size='340' side='right'caption='[[9wxs]], [[Resolution|resolution]] 1.56&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wxs]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9WXS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WXS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.56&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AG:SILVER+ION'>AG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9wxs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wxs OCA], [https://pdbe.org/9wxs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wxs RCSB], [https://www.ebi.ac.uk/pdbsum/9wxs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wxs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MDH_ECOLI MDH_ECOLI] Catalyzes the reversible oxidation of malate to oxaloacetate.[HAMAP-Rule:MF_01516]
<div style="background-color:#fffaf0;">
== 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<ref>PMID:41104151</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wxs" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Sun H]]
[[Category: Wang H]]
[[Category: Wang M]]