3F61

Crystal Structure of M. tuberculosis PknB Leu33Asp/Val222Asp double mutant in complex with ADP

3F61 の概要

• エントリーDOI: 10.2210/pdb3f61/pdb
• 分子名称: Serine/threonine-protein kinase pknB, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: protein kinase, pknb, mycobacterium tuberculosis, structural genomics, pknb kd double mutant bound to adp, tb structural genomics consortium, tbsgc, atp-binding, kinase, magnesium, metal-binding, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34060.98

構造登録者

Mieczkowski, C.A.,Alber, T.,TB Structural Genomics Consortium (TBSGC) (登録日: 2008-11-05, 公開日: 2008-12-02, 最終更新日: 2024-04-03)

主引用文献

Mieczkowski, C.,Iavarone, A.T.,Alber, T.
Auto-activation mechanism of the Mycobacterium tuberculosis PknB receptor Ser/Thr kinase.
Embo J., 27:3186-3197, 2008

PubMed Abstract: 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.

PubMed: 19008858
DOI: 10.1038/emboj.2008.236

実験手法

X-RAY DIFFRACTION (1.8 Å)