Structural Biology and Biochemistry of Cytochrome P450 Systems in Mycobacterium tuberculosis

Abstract

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.

Key Words :

• Mycobacterium tuberculosis
• Cytochrome P450
• Azole drugs
• Antitubercular therapy
• Protein structure
• Enzyme mechanism.

ABBREVIATIONS
EMB:	=	Ethambutol;
ETA:	=	Ethionamide;
FprA:	=	Flavoprotein reductase A;
INH:	=	Isoniazid;
Mtb:	=	Mycobacterium tuberculosis;
P450:	=	cytochrome P450

ACKNOWLEDGMENTS

The authors wish to acknowledge support for their research on the Mycobacterium tuberculosis P450 redox systems from the EU (6^th Framework Programme Integrated Project NM4TB) and the UK Biotechnology and Biological Sciences Research Council (BBSRC).