3ORM

Mycobacterium tuberculosis PknB kinase domain D76A mutant

3ORM の概要

• エントリーDOI: 10.2210/pdb3orm/pdb
• 関連するPDBエントリー: 1mru 1o6y 3ori 3ork 3orl 3ORM 3ORO 3ORP 3ORT
• 分子名称: Serine/threonine protein kinase, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, MANGANESE (II) ION, ... (4 entities in total)
• 機能のキーワード: structural genomics, tb structural genomics consortium, tbsgc, kinase domain, signal transduction, 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: 34052.85

構造登録者

Echols, N.,Lombana, T.N.,Alber, T.,TB Structural Genomics Consortium (TBSGC) (登録日: 2010-09-07, 公開日: 2010-12-15, 最終更新日: 2023-09-06)

主引用文献

Lombana, T.N.,Echols, N.,Good, M.C.,Thomsen, N.D.,Ng, H.L.,Greenstein, A.E.,Falick, A.M.,King, D.S.,Alber, T.
Allosteric activation mechanism of the Mycobacterium tuberculosis receptor Ser/Thr protein kinase, PknB.
Structure, 18:1667-1677, 2010

PubMed Abstract: The essential Mycobacterium tuberculosis Ser/Thr protein kinase (STPK), PknB, plays a key role in regulating growth and division, but the structural basis of activation has not been defined. Here, we provide biochemical and structural evidence that dimerization through the kinase-domain (KD) N-lobe activates PknB by an allosteric mechanism. Promoting KD pairing using a small-molecule dimerizer stimulates the unphosphorylated kinase, and substitutions that disrupt N-lobe pairing decrease phosphorylation activity in vitro and in vivo. Multiple crystal structures of two monomeric PknB KD mutants in complex with nucleotide reveal diverse inactive conformations that contain large active-site distortions that propagate > 30 Å from the mutation site. These results define flexible, inactive structures of a monomeric bacterial receptor KD and show how "back-to-back" N-lobe dimerization stabilizes the active KD conformation. This general mechanism of bacterial receptor STPK activation affords insights into the regulation of homologous eukaryotic kinases that form structurally similar dimers.

PubMed: 21134645
DOI: 10.1016/j.str.2010.09.019

実験手法

X-RAY DIFFRACTION (2.5 Å)