The preponderance of P450s in the Mycobacterium tuberculosis genome.
The genome of Mycobacterium tuberculosis (Mtb) encodes 20 different cytochrome P450 enzymes (P450s). P450s are mono-oxygenases, which are historically considered to facilitate prokaryotic usage of unusual carbon sources. However, their preponderance in Mtb strongly indicates crucial physiological functions, as does the fact that polycyclic azoles (known P450 inhibitors) have potent anti-mycobacterial effects. Recent structural and enzyme characterization data reveal novel features for at least two Mtb P450s (CYP121 and CYP51). Genome analysis, knockout studies and structural comparisons signify important roles in cell biology and pathogenesis for various P450s and redox partner enzymes in Mtb. Elucidation of structure, function and metabolic roles will be essential in targeting the P450s as an 'Achilles heel' in this major human pathogen.
McLean
Kirsty J
KJ
Manchester Interdisciplinary Biocentre, School of Chemical Engineering and Analytical Science and School of Life Sciences, University of Manchester, Jackson's Mill, Sackville Street, Manchester, UK, M60 1QD.
Clift
Daniel
D
Lewis
D Geraint
DG
Sabri
Muna
M
Balding
Philip R
PR
Sutcliffe
Michael J
MJ
Leys
David
D
Munro
Andrew W
AW
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics*; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics*; D010084:Oxidation-Reduction; D017422:Sequence Analysis, DNA
D001426:Bacterial Proteins; D007527:Isoenzymes; C464825:cytochrome P-450 CYP121; D003577:Cytochrome P-450 Enzyme System; C501935:cytochrome P-450 CYP51, Mycobacterium tuberculosis