The crystal structure of the catalytic domain of the Ser/Thr kinase PknA from M. tuberculosis shows an Src-like autoinhibited conformation

Tristan Wagner (1, 2) , Matthieu Alexandre (1, 2) , Rosario Duran (3, 4, 5) , Nathalie Barilone (1, 2) , Annemarie Wehenkel (1, 2) , Pedro M. Alzari (1, 2) , Marco Bellinzoni (1, 2)

1 Microb. Struc. (UMR_3528 / U-Pasteur_5) - Microbiologie structurale - Structural Microbiology
2 UPD7 - Université Paris Diderot - Paris 7
3 RIIP - Réseau International des Instituts Pasteur
4 Institut Pasteur de Montevideo
5 Unidad de Bioquimica y Proteomica Analiticas

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.

Keywords: Ser/Thr phosphorylation; X-ray crystallography; Autophosphorylation; Mass spectrometry; Autoinhibition; Mycobacterium tuberculosis

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]

Tristan Wagner, Matthieu Alexandre, Rosario Duran, Nathalie Barilone, Annemarie Wehenkel, et al.. The crystal structure of the catalytic domain of the Ser/Thr kinase PknA from M. tuberculosis shows an Src-like autoinhibited conformation. Proteins - Structure, Function and Bioinformatics, 2015, 83 (5), pp.982-988. ⟨10.1002/prot.24754⟩. ⟨pasteur-01175001⟩