Abstract
A gene encoding stearoyl-acyl carrier protein delta 9 desaturase (EC 1.14.99.6) from castor was expressed in Escherichia coli. The purified catalytically active enzyme contained four atoms of iron per homodimer. The desaturase was studied in two oxidation states with Mössbauer spectroscopy in applied fields up to 6.0 T. These studies show conclusively that the oxidized enzyme contains two (identical) clusters consisting of a pair of antiferromagnetically coupled (J > 60 cm-1, H = JS1.S2) Fe3+ sites. The diferric cluster exhibited absorption bands from 300 to 355 nm; addition of azide elicited a charge transfer band at 450 nm. In the presence of dithionite, the clusters were reduced to the diferrous state. Addition of stearoyl-CoA and O2 returned the clusters to the diferric state. These properties are consistent with assigning the desaturase to the class of O2-activating proteins containing diiron-oxo clusters, most notably ribonucleotide reductase and methane monooxygenase hydroxylase. Comparison of the primary structures for these three catalytically diverse proteins revealed a conserved pair of the amino acid sequence -(Asp/Glu)-Glu-Xaa-Arg-His- separated by approximately 100 amino acids. Since each of these proteins can catalyze O2-dependent cleavage of unactivated C--H bonds, we propose that these amino acid sequences represent a biological motif used for the creation of reactive catalytic intermediates. Thus, eukaryotic fatty acid desaturation may proceed via enzymatic generation of a high-valent iron-oxo species derived from the diiron cluster.
MeSH Terms
Amino Acid Sequence
Cloning, Molecular
Dithionite
Escherichia coli/genetics
Genes, Plant
Iron/analysis
Mixed Function Oxygenases/chemistry,genetics
Molecular Sequence Data
Oligodeoxyribonucleotides
Open Reading Frames
Oxidation-Reduction
Plants, Toxic
Polymerase Chain Reaction/methods
Recombinant Proteins/chemistry
Ricinus/enzymology,genetics
Sequence Homology, Amino Acid
Spectrophotometry
Spectrum Analysis
Chemicals
Oligodeoxyribonucleotides
Recombinant Proteins
Dithionite
Iron
Mixed Function Oxygenases
acyl-(acyl-carrier-protein)desaturase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Fox B G
Department of Chemistry, Carnegie Mellon University, Pittsburgh, PA 15213.
Shanklin J
Somerville C
Münck E
References (22)
22 references, click to expand
-
Enzymatic desaturation of stearyl acyl carrier protein.
J Biol Chem. 1968 Sep 10;243(17):4626-33
PMID: 4300868
-
Preliminary crystallographic data for stearoyl-acyl carrier protein desaturase from castor seed.
J Mol Biol. 1992 May 20;225(2):561-4
PMID: 1593637
-
Mössbauer spectroscopy of proteins: electron carriers.
Methods Enzymol. 1978;54:346-79
PMID: 215877
-
Subcellular localization of acyl carrier protein in leaf protoplasts of Spinacia oleracea.
Proc Natl Acad Sci U S A. 1979 Mar;76(3):1194-8
PMID: 286305
-
The stereochemistry of peroxidase catalysis.
J Biol Chem. 1980 Sep 10;255(17):8199-205
PMID: 6251047
-
Purification and characterization of the stearoyl-acyl carrier protein desaturase and the acyl-acyl carrier protein thioesterase from maturing seeds of safflower.
J Biol Chem. 1982 Oct 25;257(20):12141-7
PMID: 7118934
-
Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium.
Nature. 1985 Nov 14-20;318(6042):191-4
PMID: 3903520
-
Construction and sequence of cDNA for rat liver stearyl coenzyme A desaturase.
J Biol Chem. 1986 Oct 5;261(28):13230-5
PMID: 2428815
-
Iron superoxide dismutase. Nucleotide sequence of the gene from Escherichia coli K12 and correlations with crystal structures.
J Biol Chem. 1988 Jan 25;263(3):1555-62
PMID: 2447093
-
The biosynthesis of penicillins and cephalosporins.
Nat Prod Rep. 1988 Apr;5(2):129-45
PMID: 3145474
-
Three-dimensional structure of the free radical protein of ribonucleotide reductase.
Nature. 1990 Jun 14;345(6276):593-8
PMID: 2190093
-
Haloalkene oxidation by the soluble methane monooxygenase from Methylosinus trichosporium OB3b: mechanistic and environmental implications.
Biochemistry. 1990 Jul 10;29(27):6419-27
PMID: 2207083
-
Complete nucleotide sequence and polypeptide analysis of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600.
J Bacteriol. 1990 Dec;172(12):6826-33
PMID: 2254258
-
Stearoyl-acyl-carrier-protein desaturase from higher plants is structurally unrelated to the animal and fungal homologs.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2510-4
PMID: 2006187
-
Primary structures of the precursor and mature forms of stearoyl-acyl carrier protein desaturase from safflower embryos and requirement of ferredoxin for enzyme activity.
Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2578-82
PMID: 2006194
-
Molecular analysis of the methane monooxygenase (MMO) gene cluster of Methylosinus trichosporium OB3b.
Mol Microbiol. 1991 Feb;5(2):335-42
PMID: 1904125
-
Cloning and characterization of a Pseudomonas mendocina KR1 gene cluster encoding toluene-4-monooxygenase.
J Bacteriol. 1991 Sep;173(17):5315-27
PMID: 1885512
-
Electron transfer associated with oxygen activation in the B2 protein of ribonucleotide reductase from Escherichia coli.
J Biol Chem. 1991 Oct 15;266(29):19265-8
PMID: 1918044
-
Intrapeptide sequence homology in rubrerythrin from Desulfovibrio vulgaris: identification of potential ligands to the diiron site.
Biochem Biophys Res Commun. 1991 Nov 27;181(1):337-41
PMID: 1958203
-
NMR studies of the active site of isopenicillin N synthase, a non-heme iron(II) enzyme.
Biochemistry. 1991 Dec 17;30(50):11653-9
PMID: 1661145
-
Ligation of the diiron site of the hydroxylase component of methane monooxygenase. An electron nuclear double resonance study.
J Biol Chem. 1992 Jan 5;267(1):261-9
PMID: 1309736
-
Purification and properties of rat liver microsomal stearyl coenzyme A desaturase.
Proc Natl Acad Sci U S A. 1974 Nov;71(11):4565-9
PMID: 4373719