title: Novel substrates of Mycobacterium tuberculosis PknH Ser/Thr kinase.
abstract: PknH Ser/Thr protein kinase of Mycobacterium tuberculosis controls the expression of a variety of cell wall related enzymes and regulates the in vivo growth in mice. Therefore, we predicted that the PknH kinase could phosphorylate several substrates controlling different metabolic and physiological pathways. Using a bioinformatic approach, we identified 40 potential substrates. Two substrates were shown to be phosphorylated by recombinant PknH kinase in vitro. Point mutation studies verified that substrates are phosphorylated at the in silico-predicted sites. Kinetic studies revealed a similar relative-phosphorylation rate (V(max)) of PknH towards two new substrates and the only previously known substrate, EmbR. Unlike the EmbR protein, the Rv0681 and DacB1 proteins do not contain an FHA domain and are possible participants of new signaling pathways mediated by the PknH kinase in M. tuberculosis.
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of British Columbia, 2733 Heather St., Vancouver, BC, Canada V5Z 3J5.
authors.forename: Xingji
authors.initials: X
authors.lastname: Zheng
authors.forename: K G
authors.initials: KG
authors.lastname: Papavinasasundaram
authors.forename: Yossef
authors.initials: Y
authors.lastname: Av-Gay
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D003001:Cloning, Molecular; D019295:Computational Biology; D004789:Enzyme Activation; D004926:Escherichia coli / Q000201:enzymology; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010957:Plasmids; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D013912:Threonine / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D013912:Threonine; D012694:Serine; C484411:PknH protein, Mycobacterium tuberculosis; D017346:Protein Serine-Threonine Kinases