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FEBS Lett. 2016 Jun;590(12):1838-51. doi: 10.1002/1873-3468.12217. Epub 2016 Jun 3.

Structure-function analysis for the hydroxylation of Δ4 C21-steroids by the myxobacterial CYP260B1.

Author information

1
Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
2
Department of Structural Biology, Institute of Biophysics and Center of Human and Molecular Biology (ZHMB), Saarland University, Homburg, Germany.
3
Department of Microbial Natural Products, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research and Pharmaceutical Biotechnology, Saarland University, Saarbrücken, Germany.

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.

KEYWORDS:

CYP260B1; Sorangium cellulosum; steroid

PMID:
27177597
DOI:
10.1002/1873-3468.12217
[Indexed for MEDLINE]
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