Structure of Mycobacterium tuberculosis PknB supports a universal activation mechanism for Ser/Thr protein kinases

Nat Struct Biol. 2003 Mar;10(3):168-74. doi: 10.1038/nsb897.

Abstract

A family of eukaryotic-like Ser/Thr protein kinases occurs in bacteria, but little is known about the structures and functions of these proteins. Here we characterize PknB, a transmembrane signaling kinase from Mycobacterium tuberculosis. The intracellular PknB kinase domain is active autonomously, and the active enzyme is phosphorylated on residues homologous to regulatory phospho-acceptors in eukaryotic Ser/Thr kinases. The crystal structure of the PknB kinase domain in complex with an ATP analog reveals the active conformation. The predicted fold of the PknB extracellular domain matches the proposed targeting domain of penicillin-binding protein 2x. The structural and chemical similarities of PknB to metazoan homologs support a universal activation mechanism of Ser/Thr protein kinases in prokaryotes and eukaryotes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Carrier Proteins / chemistry
  • Conserved Sequence
  • Crystallography, X-Ray
  • Enzyme Activation / physiology
  • Eukaryotic Cells / enzymology
  • Extracellular Matrix / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mycobacterium tuberculosis / enzymology*
  • Penicillin-Binding Proteins*
  • Phosphorylation
  • Protein Conformation
  • Protein Kinase C / chemistry*
  • Protein Kinase C / metabolism
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Structural Homology, Protein

Substances

  • Bacterial Proteins
  • Carrier Proteins
  • Penicillin-Binding Proteins
  • PBP 2x protein, Streptococcus
  • Adenosine Triphosphate
  • protein kinase N
  • Protein-Serine-Threonine Kinases
  • Protein Kinase C

Associated data

  • PDB/1MRU