title: The Mycobacterium tuberculosis cytochrome P450 system.
abstract: Tuberculosis remains a leading cause of human mortality. The emergence of strains of Mycobacterium tuberculosis, the causative agent, that are resistant to the major frontline antitubercular drugs increases the urgency for the development of new therapeutic agents. Sequencing of the M. tuberculosis genome revealed the existence of 20 cytochrome P450 enzymes, some of which are potential candidates for drug targeting. The recent burst of studies reporting microarray-based gene essentiality and transcriptome analyses under in vitro, ex vivo and in vivo conditions highlight the importance of selected P450 isoforms for M. tuberculosis viability and pathogenicity. Current knowledge of the structural and biochemical properties of the M. tuberculosis P450 enzymes and their putative redox partners is reviewed, with an emphasis on findings related to their physiological function(s) as well as their potential as drug targets.
authors.affiliation: Department of Pharmaceutical Chemistry, University of California San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
authors.forename: Hugues
authors.initials: H
authors.lastname: Ouellet
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Johnston
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ortiz de Montellano
mesh_terms: D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D023281:Genomics; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D010084:Oxidation-Reduction; D010802:Phylogeny; D011487:Protein Conformation; D040901:Proteomics
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System