title: Structure-function analysis for the hydroxylation of Δ4 C21-steroids by the myxobacterial CYP260B1.
abstract: Myxobacterial CYP260B1 from Sorangium cellulosum was heterologously expressed in Escherichia coli and purified. The in vitro conversion of a small focused substrate library comprised of Δ4 C21-steroids and steroidal drugs using surrogate bovine redox partners shows that CYP260B1 is a novel steroid hydroxylase. CYP260B1 performs the regio- and stereoselective hydroxylation of the glucocorticoid cortodoxone (RSS) to produce 6β-OH-RSS. The substrate-free crystal structure of CYP260B1 (PDB 5HIW) was resolved. Docking of the tested ligands into the crystal structure suggested that the C17 hydroxy moiety and the presence of either a keto or a hydroxy group at C11 determine the selectivity of hydroxylation.
authors.affiliation: Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
authors.forename: Sandra Giovanna
authors.initials: SG
authors.lastname: Salamanca-Pinzon
authors.affiliation: Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
authors.forename: Yogan
authors.initials: Y
authors.lastname: Khatri
authors.affiliation: Department of Structural Biology, Institute of Biophysics and Center of Human and Molecular Biology (ZHMB), Saarland University, Homburg, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Carius
authors.affiliation: Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Keller
authors.affiliation: Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.affiliation: Department of Structural Biology, Institute of Biophysics and Center of Human and Molecular Biology (ZHMB), Saarland University, Homburg, Germany.
authors.forename: C Roy D
authors.initials: CR
authors.lastname: Lancaster
authors.affiliation: Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
authors.forename: Rita
authors.initials: R
authors.lastname: Bernhardt
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D003350:Cortodoxone / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006900:Hydroxylation; D062105:Molecular Docking Simulation; D009231:Myxococcales / Q000201:enzymology* / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D013250:Steroid Hydroxylases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D013250:Steroid Hydroxylases; D003350:Cortodoxone
keywords: CYP260B1; Sorangium cellulosum; steroid