Literature summary for 1.14.19.1 extracted from

Bai, Y.; McCoy, J.G.; Levin, E.J.; Sobrado, P.; Rajashankar, K.R.; Fox, B.G.; Zhou, M.
X-ray structure of a mammalian stearoyl-CoA desaturase (2015), Nature, 524, 252-256 .

Search for more literature for 1.14.19.1

Cloned(Commentary)

Cloned (Comment)	Organism
gene scd1, recombinant expression of isozyme SCD1 in Saccharomyces cerevisiae monounsaturated fatty acid auxotroph L8-14C, which allows growth in media lacking unsaturated fatty acids. Optimization of enzyme expression method	Mus musculus
gene scd3, recombinant expression of wild-type and mutant isozymes SCD3 in Saccharomyces cerevisiae monounsaturated fatty acid auxotroph L8-14C, wild-type exxpression allows growth in media lacking unsaturated fatty acids	Mus musculus

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified DELTA223 N-terminally truncated recombinant isozyme SCD1 bound to stearoyl-CoA and two ions of Zn2+ instead of Fe2+, X-ray diffraction structure determination and analysis at 2.6 A resolution, single-wavelength anomalous dispersion	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
I112A/E113L	site-directed mutagenesis, the mutation is able to convert isozyme SCD3 from exclusively a 16:0 desaturase into a predominantly 18:0 desaturase	Mus musculus
V119A/D281Q/P282S E113L	site-directed mutagenesis, the mutation of the residues which are located away from the end of the substrate tunnel, causes no change in the reaction specificity of isozyme SCD3	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
endoplasmic reticulum membrane	an integral membrane enzyme	Mus musculus	5789	-
endoplasmic reticulum membrane	isozyme SCD1 has four transmembrane helices (TM1-TM4) arranged in a cone-like shape with TM4 sandwiched between TM1 and TM2. Residues in the membrane-spanning region are largely hydrophobic, with the notable exception of a conserved arginine (Arg249) located on TM4 in the center of the cone	Mus musculus	5789	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Fe2+	a di-iron center in cofactor cytochrome b5	Mus musculus
Zn2+	incorporation of zinc instead of iron into the protein is likely an artifact of protein overexpression, and zinc remains the predominant metal species even when the growth media and purification solutions are supplemented with iron. Coordination of both zinc ions is consistent with octahedral geometry with one missing ligand. The nine histidines are highly conserved, and eight of them belong to three histidine-containing motifs (two HXXHH motifs and one HX4H motif in SCD1) that are characteristic of integral membrane desaturases	Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Mus musculus	enzyme SCD1 catalyzes the formation of a cis-double bond between the 9th and 10th carbons of stearoyl- or palmitoyl-CoA. The reaction requires molecular oxygen, which is activated by a diiron center, and cytochrome b5, which regenerates the di-iron center	?	-	?
palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+	Mus musculus	-	palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O	-	?
stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+	Mus musculus	-	oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	P13516	-	-
Mus musculus	Q99PL7	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant isozyme SCD1 from Saccharomyces cerevisiae monounsaturated fatty acid auxotroph L8-14C, incorporation of zinc instead of iron into the protein is likely an artifact of protein overexpression, and zinc remains the predominant metal species even when the growth media and purification solutions are supplemented with iron	Mus musculus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	enzyme SCD1 catalyzes the formation of a cis-double bond between the 9th and 10th carbons of stearoyl- or palmitoyl-CoA. The reaction requires molecular oxygen, which is activated by a diiron center, and cytochrome b5, which regenerates the di-iron center	Mus musculus	?	-	?
additional information	wild-type isozyme SCD3 is an exclusive 16:0 desaturase, while SCD3 enzyme mutant I112A/E113L is also active with stearoyl-CoA	Mus musculus	?	-	?
palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+	-	Mus musculus	palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O	-	?
stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+	-	Mus musculus	oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O	-	?

Subunits

Subunits	Comment	Organism
More	isozyme SCD1 has four transmembrane helices (TM1-TM4) arranged in a cone-like shape with TM4 sandwiched between TM1 and TM2, the N- and C-termini are on the cytosolic side of the membrane. On the cytosolic side, TM2 and TM4 protrude three helical turns out of the membrane and provide some of the coordinating residues for the dimetal active site. The cytosolic domain comprises 93 residues between TM2 and TM3 (C1) and the 90-residue C-terminus (C2). The C1 and C2 domains contain six and five alpha-helices, respectively. Three of the alpha-helices (AH1 on C1 and AH7 and AH9 on C2) are amphipathic and likely provide interactions between the cytosolic domain and the lipid bilayer. Structure analysis and modelling, overview. Structural role of Arg249. Structure of the SCD1 cytoplasmic domain, model	Mus musculus

Synonyms

Synonyms	Comment	Organism
SCD1	-	Mus musculus
SCD3	-	Mus musculus
stearoyl-CoA desaturase	-	Mus musculus

Cofactor

Cofactor	Comment	Organism	Structure
cytochrome b5	regenerates the di-iron center	Mus musculus

General Information

General Information	Comment	Organism
evolution	isozymes SCD1 and SCD3 share 89% primary sequence identity, but they yield remarkably different total fatty acid profiles in the recombinant yeast host cells, likely reflecting differences in their preferences for reaction with 16:0 and 18:0 substrates	Mus musculus
additional information	in SCD3, Ile112, Glu113, Ser292 and Met293 line the distal end of the substrate binding channel, Val119 is near the position of double bond formation, while Asp281 and Pro282 are on the cytoplasmic surface opposite to the CoA binding site	Mus musculus
additional information	the structure of isozyme SCD1 shows a fold comprising four transmembrane helices capped by a cytosolic domain, and a plausible pathway for lateral substrate access and product egress. The acyl chain of the bound stearoyl-CoA is enclosed in a tunnel buried in the cytosolic domain, and the geometry of the tunnel and configuration of the bound acyl chain provide a structural basis for the regioselectivity and stereospecificity of the desaturation reaction. The dimetal center is coordinated by a unique configuration of nine conserved histidine residues that implies a potentially distinct metal center and mechanism for oxygen activation, isozyme SCD1 structure analysis and modelling, overview. In SCD1, Ala108, Leu109, Ala288 and Val289 line the distal end of the substrate binding channel, Ala115 is near the position of double bond formation, while Gln277 and Ser278 are on the cytoplasmic surface opposite to the CoA binding site. Structural role of Arg249	Mus musculus
physiological function	stearoyl-CoA desaturase (SCD) introduces the first double bond into saturated fatty acyl-CoAs. Since the monounsaturated products of SCD are key precursors of membrane phospholipids, cholesterol esters, and triglycerides, SCD is pivotal in fatty acid metabolism	Mus musculus

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Release 2023.1 (January 2023)