title: Rv0132c of Mycobacterium tuberculosis encodes a coenzyme F420-dependent hydroxymycolic acid dehydrogenase.
abstract: The ability of Mycobacterium tuberculosis to manipulate and evade human immune system is in part due to its extraordinarily complex cell wall. One of the key components of this cell wall is a family of lipids called mycolic acids. Oxygenation of mycolic acids generating methoxy- and ketomycolic acids enhances the pathogenic attributes of M. tuberculosis. Thus, the respective enzymes are of interest in the research on mycobacteria. The generation of methoxy- and ketomycolic acids proceeds through intermediary formation of hydroxymycolic acids. While the methyl transferase that generates methoxymycolic acids from hydroxymycolic acids is known, hydroxymycolic acids dehydrogenase that oxidizes hydroxymycolic acids to ketomycolic acids has been elusive. We found that hydroxymycolic acid dehydrogenase is encoded by the rv0132c gene and the enzyme utilizes F420, a deazaflavin coenzyme, as electron carrier, and accordingly we called it F420-dependent hydroxymycolic acid dehydrogenase. This is the first report on the involvement of F420 in the synthesis of a mycobacterial cell envelope. Also, F420-dependent hydroxymycolic acid dehydrogenase was inhibited by PA-824, and therefore, it is a previously unknown target for this new tuberculosis drug.
authors.affiliation: Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, United States of America ; Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America.
authors.forename: Endang
authors.initials: E
authors.lastname: Purwantini
authors.affiliation: Department of Biochemistry, Virginia Tech, Blacksburg, Virginia, United States of America ; Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America ; Departments of Biological Sciences, Virginia Tech, Blacksburg, Virginia, United States of America ; Virginia Tech Carilion School of Medicine, Virginia Tech, Blacksburg, Virginia, United States of America.
authors.forename: Biswarup
authors.initials: B
authors.lastname: Mukhopadhyay
mesh_terms: D000595:Amino Acid Sequence; D000995:Antitubercular Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002473:Cell Wall / Q000201:enzymology* / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D009171:Mycolic Acids / Q000378:metabolism*; D009593:Nitroimidazoles / Q000494:pharmacology; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012256:Riboflavin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D009171:Mycolic Acids; D009593:Nitroimidazoles; C410767:pretomanid; C015084:coenzyme F420; D010088:Oxidoreductases; D012256:Riboflavin