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

被引:9
作者
Mowat, CG
Leys, D
McLean, KJ
Rivers, SL
Richmond, A
Munro, AW
Lombardia, MO
Alzari, PM
Reid, GA
Stephen, KCB
Walkinshaw, MD
机构
[1] Univ Edinburgh, Inst Cell & Mol Biol, Edinburgh EH9 3JR, Midlothian, Scotland
[2] Univ Edinburgh, Dept Chem, Edinburgh EH9 3JJ, Midlothian, Scotland
[3] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England
[4] Univ Strathclyde, Royal Coll, Dept Pure & Appl Chem, Glasgow G1 1XL, Lanark, Scotland
[5] Inst Pasteur, Struct Biochem Unit, F-75724 Paris, France
来源
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY | 2002年 / 58卷
关键词
D O I
10.1107/S0907444902002676
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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 Angstrom. Native data have been collected to 1.6 Angstrom resolution and Hg-derivative data to 2.5 Angstrom resolution using a synchrotron-radiation source.
引用
收藏
页码:704 / 705
页数:2
相关论文
共 10 条
[1]   Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence (vol 393, pg 537, 1998) [J].
Cole, ST ;
Brosch, R ;
Parkhill, J ;
Garnier, T ;
Churcher, C ;
Harris, D ;
Gordon, SV ;
Eiglmeier, K ;
Gas, S ;
Barry, CE ;
Tekaia, F ;
Badcock, K ;
Basham, D ;
Brown, D ;
Chillingworth, T ;
Conner, R ;
Davies, R ;
Devlin, K ;
Feltwell, T ;
Gentles, S ;
Hamlin, N ;
Holroyd, S ;
Hornsby, T ;
Jagels, K ;
Krogh, A ;
McLean, J ;
Moule, S ;
Murphy, L ;
Oliver, K ;
Osborne, J ;
Quail, MA ;
Rajandream, MA ;
Rogers, J ;
Rutter, S ;
Seeger, K ;
Skelton, J ;
Squares, R ;
Squares, S ;
Sulston, JE ;
Taylor, K ;
Whitehead, S ;
Barrell, BG .
NATURE, 1998, 396 (6707) :190-198
[2]   Ketoconazole-induced conformational changes in the active site of cytochrome P450eryF [J].
Cupp-Vickery, JR ;
Garcia, C ;
Hofacre, A ;
McGee-Estrada, K .
JOURNAL OF MOLECULAR BIOLOGY, 2001, 311 (01) :101-110
[3]   STRUCTURE OF CYTOCHROME P450ERYF INVOLVED IN ERYTHROMYCIN BIOSYNTHESIS [J].
CUPPVICKERY, JR ;
POULOS, TL .
NATURE STRUCTURAL BIOLOGY, 1995, 2 (02) :144-153
[4]   Azole-antifungal binding to a novel cytochrome P450 from Mycobacterium tuberculosis:: implications for treatment of tuberculosis [J].
Guardiola-Diaz, HM ;
Foster, LA ;
Mushrush, D ;
Vaz, ADN .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (12) :1463-1470
[5]   Protein engineering of cytochromes P-450 [J].
Miles, CS ;
Ost, TWB ;
Noble, MA ;
Munro, AW ;
Chapman, SK .
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1543 (02) :383-407
[6]   Processing of X-ray diffraction data collected in oscillation mode [J].
Otwinowski, Z ;
Minor, W .
MACROMOLECULAR CRYSTALLOGRAPHY, PT A, 1997, 276 :307-326
[7]   Crystal structure of cytochrome P450 14α-sterol demethylase (CYP51) from Mycobacterium tuberculosis in complex with azole inhibitors [J].
Podust, LM ;
Poulos, TL ;
Waterman, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3068-3073
[8]  
Souter A, 2000, J CHEM TECHNOL BIOT, V75, P933, DOI 10.1002/1097-4660(200010)75:10<933::AID-JCTB301>3.3.CO
[9]  
2-3
[10]  
*WHO, 1999, WHO REP GLOB TUB CON