The Mycobacterium tuberculosis cytochromes P450: physiology, biochemistry & molecular intervention

Kirsty J. McLean; James Belcher; Max D. Driscoll; Christine C. Fernandez; Duyet Le Van; Soi Bui; Marina Golovanova; Andrew W. Munro

doi:10.4155/fmc.10.216

The Mycobacterium tuberculosis cytochromes P450: physiology, biochemistry & molecular intervention

Kirsty J. McLean, James Belcher, Max D. Driscoll, Christine C. Fernandez, Duyet Le Van, Soi Bui, Marina Golovanova, Andrew W. Munro

Research output: Contribution to journal › Review article › peer-review

28 Citations (Scopus)

Abstract

The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.

Original language	English
Pages (from-to)	1339-1353
Number of pages	15
Journal	Future Medicinal Chemistry
Volume	2
Issue number	8
Early online date	23 Aug 2010
DOIs	https://doi.org/10.4155/fmc.10.216
Publication status	Published - Aug 2010
Externally published	Yes

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title = "The Mycobacterium tuberculosis cytochromes P450: physiology, biochemistry & molecular intervention",

abstract = "The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.",

keywords = "Comamonas Testosteroni, Cytochrome P-450 Cyp121, Mycobaterium Tuberculosis",

author = "McLean, {Kirsty J.} and James Belcher and Driscoll, {Max D.} and Fernandez, {Christine C.} and {Le Van}, Duyet and Soi Bui and Marina Golovanova and Munro, {Andrew W.}",

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T1 - The Mycobacterium tuberculosis cytochromes P450

T2 - physiology, biochemistry & molecular intervention

AU - McLean, Kirsty J.

AU - Belcher, James

AU - Driscoll, Max D.

AU - Fernandez, Christine C.

AU - Le Van, Duyet

AU - Bui, Soi

AU - Golovanova, Marina

AU - Munro, Andrew W.

PY - 2010/8

Y1 - 2010/8

N2 - The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.

AB - The human pathogen Mycobacterium tuberculosis (Mtb) encodes 20 cytochrome P450 (P450) enzymes. Gene essentiality for viability or host infection was demonstrated for Mtb P450s CYP128, CYP121 and CYP125. Structure/function studies on Mtb P450s revealed key roles contributing to bacterial virulence and persistence in the host. Various azole-class drugs bind with high affinity to the Mtb P450 heme and are potent Mtb antibiotics. This paper reviews the current understanding of the biochemistry of Mtb P450s, their interactions with azoles and their potential as novel Mtb drug targets. Mtb multidrug resistance is widespread and novel therapeutics are desperately needed. Simultaneous drug targeting of several Mtb P450s crucial to bacterial viability/persistence could offer a new route to effective antibiotics and minimize the development of drug resistance.

KW - Comamonas Testosteroni

KW - Cytochrome P-450 Cyp121

KW - Mycobaterium Tuberculosis

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JO - Future Medicinal Chemistry

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SN - 1756-8919

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ER -

The Mycobacterium tuberculosis cytochromes P450: physiology, biochemistry & molecular intervention

Abstract

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