期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 640, 期 -, 页码 93-101出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2017.12.018
关键词
Dioxygenase-cytochrome P450 fusion proteins; Lipidomics; Lipid metabolism; Mass spectrometry; Oxygenation mechanism; Peroxidase-cyclooxygenase superfamily
资金
- Vetenskapsradet Grant [K2013-67X-06523-31-3]
- Knut and Alice Wallenberg Foundation [KAW 2004.0123]
- Uppsala University
Pathogenic fungi express fatty acid dioxygenases (DOX) fused to cytochromes P450 with diol or allene oxide synthase activities. The orientation of the fatty acids in the active sites of DOX was investigated with amino acid conjugates of 18:3n-3 and 18:2n-6. 9S-DOX-allene oxide synthase (AOS) oxidized the Gly, Ile, and Trp derivatives at C-9, which suggests that these conjugates enter the substrate recognition site with the omega end in analogy with fatty acids bound to cyclooxygenases and coral 8R-lipoxygenase (8R-LOX). In contrast, 7,8-diol synthases (7,8-LDS), 5,8-LDS, and 8R-DOX-AOS oxidized the Gly conjugates in most case only to small amounts of metabolites, but with retention of hydrogen abstraction at C-8 and relatively minor hydrogen abstraction at C-11. The Ile and Trp conjugates were not oxidized at C-8, and often insignificantly at C-9/C-13. The 8-DOX domains of these enzymes likely position the carboxyl group of substrates at the end of the active site in analogy with plant alpha-DOX and 9-LOX. Tyr radicals of the 9S-DOX and 8R-DOX domains catalyze antarafacial hydrogen abstraction and oxygen insertion in 18:3n-3. This occurs by abstraction of the proR and proS hydrogens at C-11 and C-8, respectively, in agreement with different head to tail orientation in the active site.
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