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PDBsum entry 3f61
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References listed in PDB file
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Key reference
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Title
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Auto-Activation mechanism of the mycobacterium tuberculosis pknb receptor ser/thr kinase.
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Authors
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C.Mieczkowski,
A.T.Iavarone,
T.Alber.
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Ref.
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Embo J, 2008,
27,
3186-3197.
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PubMed id
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Abstract
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Many 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.
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