3TPB
Structure of HipA(S150A)
Summary for 3TPB
| Entry DOI | 10.2210/pdb3tpb/pdb |
| Related | 3DNT 3DNU 3DNV 3FBR 3HZI 3TPD 3TPE 3TPT 3TPV |
| Descriptor | Serine/threonine-protein kinase HipA, CHLORIDE ION, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | hipa, persistenct, multidrug tolerance, hipb, authophosphorylation, p-loop, transferase |
| Biological source | Escherichia coli |
| Total number of polymer chains | 1 |
| Total formula weight | 49588.18 |
| Authors | schumacher, M.A. (deposition date: 2011-09-07, release date: 2012-10-03, Last modification date: 2024-02-28) |
| Primary citation | Schumacher, M.A.,Min, J.,Link, T.M.,Guan, Z.,Xu, W.,Ahn, Y.H.,Soderblom, E.J.,Kurie, J.M.,Evdokimov, A.,Moseley, M.A.,Lewis, K.,Brennan, R.G. Role of Unusual P Loop Ejection and Autophosphorylation in HipA-Mediated Persistence and Multidrug Tolerance. Cell Rep, 2:518-525, 2012 Cited by PubMed Abstract: HipA is a bacterial serine/threonine protein kinase that phosphorylates targets, bringing about persistence and multidrug tolerance. Autophosphorylation of residue Ser150 is a critical regulatory mechanism of HipA function. Intriguingly, Ser150 is not located on the activation loop, as are other kinases; instead, it is in the protein core, where it forms part of the ATP-binding "P loop motif." How this buried residue is phosphorylated and regulates kinase activity is unclear. Here, we report multiple structures that reveal the P loop motif's exhibition of a remarkable "in-out" conformational equilibrium, which allows access to Ser150 and its intermolecular autophosphorylation. Phosphorylated Ser150 stabilizes the "out state," which inactivates the kinase by disrupting the ATP-binding pocket. Thus, our data reveal a mechanism of protein kinase regulation that is vital for multidrug tolerance and persistence, as kinase inactivation provides the critical first step in allowing dormant cells to revert to the growth phenotype and to reinfect the host. PubMed: 22999936DOI: 10.1016/j.celrep.2012.08.013 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.88 Å) |
Structure validation
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