3TPE: The phipa p3121 structure

Citation:
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.
PDB ID: 3TPEDownload
MMDB ID: 103435
PDB Deposition Date: 2011/9/7
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Similar Structures:
Biological Unit for 3TPE: monomeric; determined by author
Molecular Components in 3TPE
Label Count Molecule
Protein (1 molecule)
1
Serine/threonine-protein Kinase Hipa(Gene symbol: hipA)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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