Structural biology and biochemistry of cytochrome P450 systems in Mycobacterium tuberculosis.
The global spread of tuberculosis (TB) has been fuelled by the development of strains of the causative bacterium (Mycobacterium tuberculosis, Mtb) that are resistant to all the leading drugs. New TB therapies are desperately needed, but recent genome sequence, genetic and protein characterization studies have helped identify novel Mtb drug targets and key biochemical pathways for strategic intervention. Of particular interest are the multiple cytochrome P450 (P450) enzymes encoded in the Mtb genome. Structural, biochemical and mechanistic studies on these systems have demonstrated their potential as antitubercular targets, as well as revealing novel aspects of P450 form and function.
McLean
Kirsty J
KJ
Manchester Interdisciplinary Biocentre, The University of Manchester, Faculty of Life Sciences, Manchester, M1, UK. Kirsty.McLean@Manchester.ac.uk
Munro
Andrew W
AW
D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D007527:Isoenzymes / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System