Structural highlights
Publication Abstract from PubMed
GfsF is a multifunctional P450 monooxygenase that catalyzes the epoxidation and subsequent hydroxylation in the biosynthesis of macrolide polyketide FD-891. Here, we describe the biochemical and structural analysis of GfsF. To obtain the structural basis of a dual functional reaction, we determined the crystal structure of ligand-free GfsF, which revealed GfsF to have a predominantly hydrophobic substrate binding pocket. The docking models in conjunction with the results of the enzymatic assay with substrate analogs as well as site-directed mutagenesis suggested two distinct substrate binding modes for epoxidation and hydroxylation reactions, which explained how GfsF regulates the order of two oxidative reactions. These findings provide new insights into the reaction mechanism of multifunctional P450 monooxygenases.
Substrate recognition by a dual functional P450 monooxygenase GfsF involved in FD-891 biosynthesis.,Eguchi T, Miyanaga A, Takayanagi R, Furuya T, Kawamata A, Itagaki T, Iwabuchi Y, Kanoh N, Kudo F Chembiochem. 2017 Sep 4. doi: 10.1002/cbic.201700429. PMID:28869713[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Eguchi T, Miyanaga A, Takayanagi R, Furuya T, Kawamata A, Itagaki T, Iwabuchi Y, Kanoh N, Kudo F. Substrate recognition by a dual functional P450 monooxygenase GfsF involved in FD-891 biosynthesis. Chembiochem. 2017 Sep 4. doi: 10.1002/cbic.201700429. PMID:28869713 doi:http://dx.doi.org/10.1002/cbic.201700429
