title: Co-induction of methyltransferase Rv0560c by naphthoquinones and fibric acids suggests attenuation of isoprenoid quinone action in Mycobacterium tuberculosis.
abstract: The superoxide generator menadione was previously demonstrated as an inducer of growth stage dependent protein patterns in Mycobacterium tuberculosis. The present study refines this observation by characterizing a novel 27-kDa protein that had not been observed in previous studies relying on younger cultures. A very similar response, based on two-dimensional gel electrophoretic analyses, was induced by the closely related naphthoquinone plumbagin. The 27-kDa protein was also induced by the pro-oxidant peroxisome proliferator gemfibrozil and to a lesser extent by the structurally related compounds fenofibrate and clofibrate. N-terminal sequence data of proteolytic fragments from the 27-kDa protein demonstrated its identity with protein Rv0560c, previously demonstrated to be inducible by salicylate, which also possesses peroxisome proliferating properties. Protein Rv0560c bears three conserved motifs characteristic of S-adenosylmethionine-dependent methyltransferases. Further sequence similarities suggest a function in the bio syn thesis of isoprenoid compounds, e.g., tocopherol, ubiquinone, and sterols. Such involvement is supported by the recognized yet unexplained widespread interference of menadione, salicylate, and fibrates with the isoprenoid quinones ubiquinone, menaquinone, and vitamin K. Induction of Rv0560c by fibrates, salicylate, and naphthoquinones is thus suggested to be caused by action on the plasma membrane, reminiscent of cytochrome P450BM-3 induction by fibrates in Bacillus megaterium, which catalyzes the hydroxylation of fatty acids and thus modulates membrane properties.
authors.affiliation: Department of Microbiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78285-7739, USA. garbetr@rite.or.jp
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Garbe
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001410:Bacillus megaterium / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology*; D017124:Conserved Sequence; D015180:Electrophoresis, Gel, Two-Dimensional; D020536:Enzyme Activators / Q000494:pharmacology; D015248:Gemfibrozil / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D005798:Genes, Bacterial; D008780:Methyltransferases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D009285:Naphthoquinones / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D020536:Enzyme Activators; D009285:Naphthoquinones; D002995:Clofibric Acid; D008780:Methyltransferases; D015248:Gemfibrozil; C014758:plumbagin