PMID- 24060467
OWN - NLM
STAT- MEDLINE
DCOM- 20131212
LR  - 20131021
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 539
IP  - 1
DP  - 2013 Nov 1
TI  - 7,8- and 5,8-Linoleate diol synthases support the heterolytic scission of 
      oxygen-oxygen bonds by different amide residues.
PG  - 87-91
LID - S0003-9861(13)00286-5 [pii]
LID - 10.1016/j.abb.2013.09.010 [doi]
AB  - Linoleate diol synthases (LDS) are fungal dioxygenase-cytochrome P450 fusion 
      enzymes. They oxidize 18:2n-6 sequentially to 8R-hydroperoxylinoleic acid 
      (8R-HPODE) and 7S,8S- or 5S,8R-dihydroxylinoleic acids (DiHODE) by intramolecular 
      oxygen transfer. The P450 domains contain a conserved sequence, 
      Ala-Asn-Gln-Xaa-Gln, presumably located in the I-helices. The Asn938Leu 
      replacement of 7,8-LDS of Gaeumannomyces graminis virtually abolished and the 
      Asn938Asp and Asn938Gln replacements reduced the hydroperoxide isomerase 
      activity. Gln941Leu and Gln941Glu substitutions had little effects. Replacements 
      of the homologous Asn(887) and Gln(890) residues of 5,8-LDS of Aspergillus 
      fumigatus yielded the opposite results. Asn887Leu and Asn887Gln of 5,8-LDS 
      retained 5,8-DiHODE as the main metabolite with an increased formation of 6,8- 
      and 8,11-DiHODE, whereas Gln890Leu almost abolished the 5,8-LDS activity. 
      Replacement of Gln(890) with Glu also retained 5,8-DiHODE as the main product, 
      but shifted oxygenation from C-5 to C-7 and C-11 and to formation of 
      epoxyalcohols by homolytic scission of 8R-HPODE. P450 hydroxylases usually 
      contain an "acid-alcohol" pair in the I-helices for the heterolytic scission of 
      O2 and formation of compound I (Por(+) Fe(IV)=O) and water. The function of the 
      acid-alcohol pair appears to be replaced by two different amide residues, 
      Asn(938) of 7,8-LDS and Gln(890) of 5,8-LDS, for heterolysis of 8R-HPODE to 
      generate compound I.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Hoffmann, Inga
AU  - Hoffmann I
AD  - Department of Pharmaceutical Biosciences, Division of Biochemical Pharmacology, 
      Uppsala Biomedical Center, Uppsala University, SE-75124 Uppsala, Sweden.
FAU - Oliw, Ernst H
AU  - Oliw EH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130920
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Amides)
RN  - EC 1.13.- (Oxygenases)
RN  - EC 1.14.99.- (linoleate diol synthase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Amides/*chemistry
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Ascomycota/enzymology
MH  - Aspergillus fumigatus/enzymology
MH  - Computational Biology
MH  - Conserved Sequence
MH  - Models, Molecular
MH  - Oxygen/*chemistry
MH  - Oxygenases/*chemistry/genetics/metabolism
MH  - Protein Structure, Secondary
OTO - NOTNLM
OT  - Heme peroxidase
OT  - Mutagenesis site-specific
OT  - Oxygenation mechanism
OT  - Oxylipin biosynthesis
OT  - P450 class III
OT  - Prostacyclin synthase
EDAT- 2013/09/26 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/09/25 06:00
PHST- 2013/07/22 00:00 [received]
PHST- 2013/09/11 00:00 [revised]
PHST- 2013/09/13 00:00 [accepted]
PHST- 2013/09/25 06:00 [entrez]
PHST- 2013/09/26 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - S0003-9861(13)00286-5 [pii]
AID - 10.1016/j.abb.2013.09.010 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2013 Nov 1;539(1):87-91. doi: 10.1016/j.abb.2013.09.010. 
      Epub 2013 Sep 20.