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

Christopher Mowat (1) , David Leys (1) , Kirsty Mclean (2) , Stuart Rivers (1) , Alison Richmond (3) , Andrew Munro (2) , Miguel Ortiz Lombardia (4) , Pedro Alzari (4) , Graeme Reid (1) , Stephen Chapman (1) , Malcolm Walkinshaw (1)

1 Edin. - University of Edinburgh
2 University of Leicester
3 University of Strathclyde [Glasgow]
4 Biochimie Structurale

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 P6(1)22 or P6(5)22, with unit-cell parameters a = b = 78.3, c = 265.6 A. Native data have been collected to 1.6 A resolution and Hg-derivative data to 2.5 A resolution using a synchrotron-radiation source.

Mots clés: cytochrome P450

Domaines: Cristallographie; Biologie structurale [q-bio.BM]; Biochimie, Biologie Moléculaire; Bio-informatique [q-bio.QM]; Biophysique [physics.bio-ph]; Biologie cellulaire

Christopher Mowat, David Leys, Kirsty Mclean, Stuart Rivers, Alison Richmond, et al.. Crystallization and preliminary crystallographic analysis of a novel cytochrome P450 from Mycobacterium tuberculosis. Acta crystallographica Section D : Structural biology [1993-..], 2002, 58 (4), pp.704-705. ⟨10.1107/s0907444902002676⟩. ⟨pasteur-03144700⟩