3ORO

Mycobacterium tuberculosis PknB kinase domain L33D mutant (crystal form 4)

Summary for 3ORO

• Entry DOI: 10.2210/pdb3oro/pdb
• Related: 1mru 1o6y 3ORP 3ORT 3ori 3ork 3orl 3orm
• Descriptor: Serine/threonine protein kinase, PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (4 entities in total)
• Functional Keywords: structural genomics, tb structural genomics consortium, tbsgc, kinase domain, signal transduction, transferase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 1
• Total formula weight: 34251.14

Authors

Good, M.C.,Echols, N.,Lombana, T.N.,Alber, T.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2010-09-07, release date: 2010-12-15, Last modification date: 2023-09-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.9 Å)