3f69
Crystal structure of the Mycobacterium tuberculosis PknB mutant kinase domain in complex with KT5720Crystal structure of the Mycobacterium tuberculosis PknB mutant kinase domain in complex with KT5720
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMany Ser/Thr protein kinases are activated by autophosphorylation, but the mechanism of this process has not been defined. We determined the crystal structure of a mutant of the Ser/Thr kinase domain (KD) of the mycobacterial sensor kinase PknB in complex with an ATP competitive inhibitor and discovered features consistent with an activation complex. The complex formed an asymmetric dimer, with the G helix and the ordered activation loop of one KD in contact with the G helix of the other. The activation loop of this putative 'substrate' KD was disordered, with the ends positioned at the entrance to the partner KD active site. Single amino-acid substitutions in the G-helix interface reduced activation-loop phosphorylation, and multiple replacements abolished KD phosphorylation and kinase activation. Phosphorylation of an inactive mutant KD was reduced by G-helix substitutions in both active and inactive KDs, as predicted by the idea that the asymmetric dimer mimics a trans-autophosphorylation complex. These results support a model in which a structurally and functionally asymmetric, 'front-to-front' association mediates autophosphorylation of PknB and homologous kinases. Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase.,Mieczkowski C, Iavarone AT, Alber T EMBO J. 2008 Dec 3;27(23):3186-97. Epub 2008 Nov 13. PMID:19008858[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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