Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis

Christopher G. Mowat; David Leys; Kirsty J. McLean; Stuart L. Rivers; Alison Richmond; Andrew W. Munro; Miguel Ortiz Lombardia; Pedro M. Alzari; Graeme A. Reid; Stephen K. Chapman; Malcolm D. Walkinshaw

doi:10.1107/S0907444902002676

Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis

Christopher G. Mowat, David Leys, Kirsty J. McLean, Stuart L. Rivers, Alison Richmond, Andrew W. Munro, Miguel Ortiz Lombardia, Pedro M. Alzari, Graeme A. Reid, Stephen K. Chapman, Malcolm D. Walkinshaw

Research output: Contribution to journal › Article › peer-review

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Abstract

The product of the Rv2276 gene of Mycobacterium tuberculosis is a cytochrome P450 (P450 MT2, CYP121) which has been shown to bind tightly to a range of azole-based antifungal drugs (e.g. miconazole, clotrimazole). These drugs are potent inhibitors of mycobacterial growth, suggesting that P450 MT2 (CYP121) may be a potential drug target. The enzyme has been overexpressed in Escherichia coli and crystallized by the hanging-drop method. Crystals of P450 MT2 (CYP121) belong to the hexagonal space group P6₁22 or P6₅22, with unit-cell parameters a = b = 78.3, c = 265.6 Å. Native data have been collected to 1.6 Å resolution and Hg-derivative data to 2.5 Å resolution using a synchrotron-radiation source.

Original language	English
Pages (from-to)	704-705
Number of pages	2
Journal	Acta Crystallographica Section D: Biological Crystallography
Volume	58
Issue number	4
DOIs	https://doi.org/10.1107/S0907444902002676
Publication status	Published - 1 Apr 2002
Externally published	Yes

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Mowat, C. G., Leys, D., McLean, K. J., Rivers, S. L., Richmond, A., Munro, A. W., Ortiz Lombardia, M., Alzari, P. M., Reid, G. A., Chapman, S. K., & Walkinshaw, M. D. (2002). Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis. Acta Crystallographica Section D: Biological Crystallography, 58(4), 704-705. https://doi.org/10.1107/S0907444902002676

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title = "Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis",

abstract = "The product of the Rv2276 gene of Mycobacterium tuberculosis is a cytochrome P450 (P450 MT2, CYP121) which has been shown to bind tightly to a range of azole-based antifungal drugs (e.g. miconazole, clotrimazole). These drugs are potent inhibitors of mycobacterial growth, suggesting that P450 MT2 (CYP121) may be a potential drug target. The enzyme has been overexpressed in Escherichia coli and crystallized by the hanging-drop method. Crystals of P450 MT2 (CYP121) belong to the hexagonal space group P6122 or P6522, with unit-cell parameters a = b = 78.3, c = 265.6 {\AA}. Native data have been collected to 1.6 {\AA} resolution and Hg-derivative data to 2.5 {\AA} resolution using a synchrotron-radiation source.",

keywords = "Cytochrome P450",

author = "Mowat, {Christopher G.} and David Leys and McLean, {Kirsty J.} and Rivers, {Stuart L.} and Alison Richmond and Munro, {Andrew W.} and {Ortiz Lombardia}, Miguel and Alzari, {Pedro M.} and Reid, {Graeme A.} and Chapman, {Stephen K.} and Walkinshaw, {Malcolm D.}",

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doi = "10.1107/S0907444902002676",

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Mowat, CG, Leys, D, McLean, KJ, Rivers, SL, Richmond, A, Munro, AW, Ortiz Lombardia, M, Alzari, PM, Reid, GA, Chapman, SK & Walkinshaw, MD 2002, 'Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis', Acta Crystallographica Section D: Biological Crystallography, vol. 58, no. 4, pp. 704-705. https://doi.org/10.1107/S0907444902002676

TY - JOUR

T1 - Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis

AU - Mowat, Christopher G.

AU - Leys, David

AU - McLean, Kirsty J.

AU - Rivers, Stuart L.

AU - Richmond, Alison

AU - Munro, Andrew W.

AU - Ortiz Lombardia, Miguel

AU - Alzari, Pedro M.

AU - Reid, Graeme A.

AU - Chapman, Stephen K.

AU - Walkinshaw, Malcolm D.

PY - 2002/4/1

Y1 - 2002/4/1

N2 - The product of the Rv2276 gene of Mycobacterium tuberculosis is a cytochrome P450 (P450 MT2, CYP121) which has been shown to bind tightly to a range of azole-based antifungal drugs (e.g. miconazole, clotrimazole). These drugs are potent inhibitors of mycobacterial growth, suggesting that P450 MT2 (CYP121) may be a potential drug target. The enzyme has been overexpressed in Escherichia coli and crystallized by the hanging-drop method. Crystals of P450 MT2 (CYP121) belong to the hexagonal space group P6122 or P6522, with unit-cell parameters a = b = 78.3, c = 265.6 Å. Native data have been collected to 1.6 Å resolution and Hg-derivative data to 2.5 Å resolution using a synchrotron-radiation source.

AB - The product of the Rv2276 gene of Mycobacterium tuberculosis is a cytochrome P450 (P450 MT2, CYP121) which has been shown to bind tightly to a range of azole-based antifungal drugs (e.g. miconazole, clotrimazole). These drugs are potent inhibitors of mycobacterial growth, suggesting that P450 MT2 (CYP121) may be a potential drug target. The enzyme has been overexpressed in Escherichia coli and crystallized by the hanging-drop method. Crystals of P450 MT2 (CYP121) belong to the hexagonal space group P6122 or P6522, with unit-cell parameters a = b = 78.3, c = 265.6 Å. Native data have been collected to 1.6 Å resolution and Hg-derivative data to 2.5 Å resolution using a synchrotron-radiation source.

KW - Cytochrome P450

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ER -

Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis

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