title: The crystal structure of the catalytic domain of the ser/thr kinase PknA from M. tuberculosis shows an Src-like autoinhibited conformation.
abstract: Signal transduction mediated by Ser/Thr phosphorylation in Mycobacterium tuberculosis has been intensively studied in the last years, as its genome harbors eleven genes coding for eukaryotic-like Ser/Thr kinases. Here we describe the crystal structure and the autophosphorylation sites of the catalytic domain of PknA, one of two protein kinases essential for pathogen's survival. The structure of the ligand-free kinase domain shows an auto-inhibited conformation similar to that observed in human Tyr kinases of the Src-family. These results reinforce the high conservation of structural hallmarks and regulation mechanisms between prokaryotic and eukaryotic protein kinases.
authors.affiliation: Institut Pasteur, Unité De Microbiologie Structurale, Paris, 75724, France; CNRS UMR 3528, Paris, 75724, France; Université Paris Diderot, Sorbonne Paris Cité, Microbiologie Structurale, Paris, 75724, France.
authors.forename: Tristan
authors.initials: T
authors.lastname: Wagner
authors.forename: Matthieu
authors.initials: M
authors.lastname: Alexandre
authors.forename: Rosario
authors.initials: R
authors.lastname: Duran
authors.forename: Nathalie
authors.initials: N
authors.lastname: Barilone
authors.forename: Annemarie
authors.initials: A
authors.lastname: Wehenkel
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
authors.forename: Marco
authors.initials: M
authors.lastname: Bellinzoni
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004789:Enzyme Activation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; C451020:PknA protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases
keywords: Mycobacterium tuberculosis; Ser/Thr phosphorylation; X-ray crystallography; autoinhibition; autophosphorylation; mass spectrometry