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Structure–function analysis for the hydroxylation of Δ4 C21‐steroids by the myxobacterial CYP260B1
Author(s) -
SalamancaPinzon Sandra Giovanna,
Khatri Yogan,
Carius Yvonne,
Keller Lena,
Müller Rolf,
Lancaster C. Roy D.,
Bernhardt Rita
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12217
Subject(s) - hydroxylation , chemistry , function (biology) , stereochemistry , biochemistry , biology , microbiology and biotechnology , enzyme
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.