9k3g
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of Sortase A from Streptococcus pyogenes in complex with T10== | |
| + | <StructureSection load='9k3g' size='340' side='right'caption='[[9k3g]], [[Resolution|resolution]] 1.23Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[9k3g]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9K3G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9K3G 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]] 1.23Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EEN:[4-[[2,4,6-tris(oxidanylidene)-1,3-diazinan-5-ylidene]methyl]phenyl]+(2~{S})-4-methyl-2-(phenylmethoxycarbonylamino)pentanoate'>A1EEN</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=9k3g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9k3g OCA], [https://pdbe.org/9k3g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9k3g RCSB], [https://www.ebi.ac.uk/pdbsum/9k3g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9k3g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/A0A4U7I1I9_STRPY A0A4U7I1I9_STRPY] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Sortase A (SrtA), a cysteine transpeptidase critical for surface protein anchoring in Gram-positive pathogens, represents an attractive antivirulence target. While covalent SrtA inhibitors show therapeutic potential, existing compounds lack species selectivity. Through structure-guided design, we developed T10, a covalent inhibitor selectively targeting Streptococcus pyogenes SrtA (SpSrtA) over Staphylococcus aureus SrtA (SaSrtA). Molecular docking revealed that shortening a "C=C" bond in lead compound ML346 eliminated SaSrtA inhibition due to steric hindrance from W194, while maintaining SpSrtA binding. X-ray crystallography confirmed T10's covalent modification of Cys208 in SpSrtA. T10 demonstrated two fold enhanced inhibitory potency and species-specific disruption of M-protein anchoring and biofilm formation in Streptococcus pyogenes, without affecting Staphylococcus aureus viability. In a Galleria mellonella infection model, T10 conferred potent protection against lethal infection. This work demonstrates the development of narrow-spectrum antivirulence agents through a structure-based rational strategy. | ||
| - | + | Structure-Based Development of a Covalent Inhibitor Targeting Streptococcus Pyogenes over Staphylococcus Aureus Sortase A.,Zhou H, Yuan Z, Guan XN, Yue C, Wu W, Lan L, Gan J, Zhang T, Yang CG Chemistry. 2025 Mar 12:e202500464. doi: 10.1002/chem.202500464. PMID:40072260<ref>PMID:40072260</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Gan | + | <div class="pdbe-citations 9k3g" style="background-color:#fffaf0;"></div> |
| - | [[Category: Yang | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Streptococcus pyogenes]] | ||
| + | [[Category: Gan J]] | ||
| + | [[Category: Yang CG]] | ||
Current revision
Crystal structure of Sortase A from Streptococcus pyogenes in complex with T10
| |||||||||||
