title: MT FdR: a ferredoxin reductase from M. tuberculosis that couples to MT CYP51.
abstract: We report the molecular cloning, expression and partial characterization of MT FdR, an FAD-associated flavoprotein, from Mycobacterium tuberculosis similar to the oxygenase-coupled NADH-dependent ferredoxin reductases (ONFR). We establish, through kinetic and spectral analysis, that MT FdR preferentially uses NADH as cofactor. Furthermore, MT FdR forms a complex with mycobacterial ferredoxin (MT Fdx) and MT CYP51, a cytochrome P450 (CYP) from M. tuberculosis that is similar to lanosterol 14alpha-demethylase isozymes. This reconstituted system transfers electrons from the cofactor to the heme iron of MT CYP51 and effects the demethylation of lanosterol.
authors.affiliation: Department of Biology, Trinity College, 300 Summit Street Hartford, CT 06106, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Zanno
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kwiatkowski
authors.forename: Alfin D N
authors.initials: AD
authors.lastname: Vaz
authors.forename: Hebe M
authors.initials: HM
authors.lastname: Guardiola-Diaz
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004579:Electron Transport; D005288:Ferredoxins / Q000378:metabolism; D007700:Kinetics; D007810:Lanosterol / Q000378:metabolism; D046912:Multiprotein Complexes; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013057:Spectrum Analysis
chemical_list: D001426:Bacterial Proteins; D005288:Ferredoxins; D046912:Multiprotein Complexes; D009243:NAD; D007810:Lanosterol; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C501935:cytochrome P-450 CYP51, Mycobacterium tuberculosis; C028878:ferredoxin-NAD+ reductase