9YMT
Staphylococcus aureus serine/threonine kinase Stk1 with inhibitor GW779439X
This is a non-PDB format compatible entry.
Summary for 9YMT
| Entry DOI | 10.2210/pdb9ymt/pdb |
| Descriptor | Serine/Threonine Kinase, (4M)-N-[4-(4-methylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-4-[(8R)-pyrazolo[1,5-b]pyridazin-3-yl]pyrimidin-2-amine, BENZAMIDINE, ... (5 entities in total) |
| Functional Keywords | kinase, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor |
| Biological source | Staphylococcus aureus subsp. aureus N315 |
| Total number of polymer chains | 1 |
| Total formula weight | 34615.05 |
| Authors | Mosimann, W.A.,Strynadka, N.C.J.,Worrall, L.J. (deposition date: 2025-10-10, release date: 2026-03-11) |
| Primary citation | Chatterjee, S.,Poon, R.,Satishkumar, N.,Mosimann, W.,Hayatnagarkar, V.,Hemmadi, V.,Kuhn, S.,Chatterjee, A.,Worrall, L.,Manes, N.,Alexander, J.A.,Lack, J.,Chambers, H.,Nita-Lazar, A.,Strynadka, N. Stk1 is required for BlaR1-mediated broad-spectrum beta-lactam resistance in epidemic-causing strains of Staphylococcus aureus. Res Sq, 2026 Cited by PubMed Abstract: Sensory induction of expression plays a pivotal role in mediating broad-spectrum β-lactam resistance (BBR) of MRSA. In contemporary MRSA isolates, sensory induction of BBR originates at the membrane-localized BlaR1, which, upon detection of β-lactam drugs, triggers a signal transduction cascade that promotes 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 -mediated BBR. Our results demonstrated that targeting Stk1 could potentiate synthetic lethality to β-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. PubMed: 41743328DOI: 10.21203/rs.3.rs-8331258/v1 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.07 Å) |
Structure validation
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