7v6k
From Proteopedia
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==Crystal structure of Sortase A from Streptococcus pyogenes in complex with ML346== | ==Crystal structure of Sortase A from Streptococcus pyogenes in complex with ML346== | ||
| - | <StructureSection load='7v6k' size='340' side='right'caption='[[7v6k]]' scene=''> | + | <StructureSection load='7v6k' size='340' side='right'caption='[[7v6k]], [[Resolution|resolution]] 1.57Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V6K FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7v6k]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7V6K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7V6K FirstGlance]. <br> |
| - | </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=7v6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v6k OCA], [https://pdbe.org/7v6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v6k RCSB], [https://www.ebi.ac.uk/pdbsum/7v6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v6k ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5TI:5-[3-(4-methoxyphenyl)prop-2-enylidene]-1,3-diazinane-2,4,6-trione'>5TI</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7v6k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7v6k OCA], [https://pdbe.org/7v6k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7v6k RCSB], [https://www.ebi.ac.uk/pdbsum/7v6k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7v6k ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The housekeeping sortase A (SrtA), a membrane-associated cysteine transpeptidase, is responsible for anchoring surface proteins to the cell wall peptidoglycan in Gram-positive bacteria. This process is essential for the regulation of bacterial virulence and pathogenicity. Therefore, SrtA is considered to be an ideal target for antivirulence therapy. In this study, we report that ML346, a compound with a barbituric acid and cinnamaldehyde scaffold, functions as an irreversible inhibitor of Staphylococcus aureus SrtA (SaSrtA) and Streptococcus pyogenes SrtA (SpSrtA) in vitro at low micromolar concentrations. According to our X-ray crystal structure of the SpSrtADeltaN81/ML346 complex (Protein Data Bank ID: 7V6K), ML346 covalently modifies the thiol group of Cys208 in the active site of SpSrtA. Importantly, ML346 significantly attenuated the virulence phenotypes of S. aureus and exhibited inhibitory effects on Galleria mellonella larva infection caused by S. aureus. Collectively, our results indicate that ML346 has potential for development as a covalent antivirulence agent for treating S. aureus infections, including methicillin-resistant S. aureus. | ||
| + | |||
| + | Covalent sortase A inhibitor ML346 prevents Staphylococcus aureus infection of Galleria mellonella.,Guan XN, Zhang T, Yang T, Dong Z, Yang S, Lan L, Gan J, Yang CG RSC Med Chem. 2021 Nov 1;13(2):138-149. doi: 10.1039/d1md00316j. eCollection 2022, Feb 23. PMID:35308030<ref>PMID:35308030</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7v6k" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Gan J]] | + | [[Category: Gan, J]] |
| - | [[Category: Yang | + | [[Category: Yang, C G]] |
| + | [[Category: Hydrolase]] | ||
| + | [[Category: Sortase some]] | ||
| + | [[Category: Transpetidase]] | ||
Revision as of 11:57, 27 April 2022
Crystal structure of Sortase A from Streptococcus pyogenes in complex with ML346
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