9ymt: Difference between revisions
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==Staphylococcus aureus serine/threonine kinase Stk1 with inhibitor GW779439X== | |||
<StructureSection load='9ymt' size='340' side='right'caption='[[9ymt]], [[Resolution|resolution]] 2.07Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9ymt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_N315 Staphylococcus aureus subsp. aureus N315]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9YMT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YMT 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]] 2.07Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1CYJ:~{N}-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-4-pyrazolo[1,5-b]pyridazin-3-yl-pyrimidin-2-amine'>A1CYJ</scene>, <scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=9ymt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ymt OCA], [https://pdbe.org/9ymt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ymt RCSB], [https://www.ebi.ac.uk/pdbsum/9ymt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ymt ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Sensory induction of mecA expression plays a pivotal role in mediating broad-spectrum beta-lactam resistance (BBR) of MRSA. In contemporary MRSA isolates, sensory induction of BBR originates at the membrane-localized BlaR1, which, upon detection of beta-lactam drugs, triggers a signal transduction cascade that promotes mecA induction. We hereby showed that phosphorylation of BlaR1, mediated through the serine-threonine kinase, Stk1, stabilizes its membrane spanning state and localization, allowing for proper drug sensing and subsequent signal transduction events to occur, culminating in mecA-mediated BBR. Our results demonstrated that targeting Stk1 could potentiate synthetic lethality to beta-lactams in the majority of naturally isolated strains of MRSA. We also presented the structural and kinetic basis for a Stk1-inhibitor complex that could enable rational design of Stk1 directed anti-MRSA therapeutics in the future. Our results reveal a unique and hitherto unknown role of the STK signaling pathway in bacterial protein stabilization in the cytosolic membrane. | |||
Stk1 is required for BlaR1-mediated broad-spectrum beta-lactam resistance in epidemic-causing strains of Staphylococcus aureus.,Chatterjee S, Poon R, Satishkumar N, Mosimann W, Hayatnagarkar V, Hemmadi V, Kuhn S, Chatterjee A, Worrall L, Manes N, Alexander JA, Lack J, Chambers H, Nita-Lazar A, Strynadka N Res Sq [Preprint]. 2026 Jan 12:rs.3.rs-8331258. doi: 10.21203/rs.3.rs-8331258/v1. PMID:41743328<ref>PMID:41743328</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9ymt" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus subsp. aureus N315]] | |||
[[Category: Mosimann WA]] | |||
[[Category: Strynadka NCJ]] | |||
[[Category: Worrall LJ]] | |||
