|
|
| Line 3: |
Line 3: |
| | <StructureSection load='4zyo' size='340' side='right'caption='[[4zyo]], [[Resolution|resolution]] 3.25Å' scene=''> | | <StructureSection load='4zyo' size='340' side='right'caption='[[4zyo]], [[Resolution|resolution]] 3.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zyo]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zyo]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZYO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=ST9:STEAROYL-COENZYME+A'>ST9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=ST9:STEAROYL-COENZYME+A'>ST9</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCD ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4zyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zyo OCA], [https://pdbe.org/4zyo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zyo RCSB], [https://www.ebi.ac.uk/pdbsum/4zyo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zyo ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Stearoyl-CoA_9-desaturase Stearoyl-CoA 9-desaturase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.19.1 1.14.19.1] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4zyo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zyo OCA], [http://pdbe.org/4zyo PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zyo RCSB], [http://www.ebi.ac.uk/pdbsum/4zyo PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zyo ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ACOD_HUMAN ACOD_HUMAN]] Terminal component of the liver microsomal stearyl-CoA desaturase system, that utilizes O(2) and electrons from reduced cytochrome b5 to catalyze the insertion of a double bond into a spectrum of fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA. | + | [https://www.uniprot.org/uniprot/SCD_HUMAN SCD_HUMAN] Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates (PubMed:15907797, PubMed:18765284). Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:15907797, PubMed:18765284). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids (PubMed:15610069). Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation (By similarity). Plays an important role in body energy homeostasis (By similarity). Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (By similarity).[UniProtKB:P13516]<ref>PMID:15610069</ref> <ref>PMID:15907797</ref> <ref>PMID:18765284</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 24: |
Line 22: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Stearoyl-CoA 9-desaturase]]
| + | [[Category: Klein MG]] |
| - | [[Category: Klein, M G]] | + | [[Category: Lane W]] |
| - | [[Category: Lane, W]] | + | [[Category: Levin I]] |
| - | [[Category: Levin, I]] | + | [[Category: Li K]] |
| - | [[Category: Li, K]] | + | [[Category: Sang B-C]] |
| - | [[Category: Sang, B C]] | + | [[Category: Snell G]] |
| - | [[Category: Snell, G]] | + | [[Category: Wang H]] |
| - | [[Category: Wang, H]] | + | [[Category: Zou H]] |
| - | [[Category: Zou, H]] | + | |
| - | [[Category: Desaturase]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| Structural highlights
Function
SCD_HUMAN Stearoyl-CoA desaturase that utilizes O(2) and electrons from reduced cytochrome b5 to introduce the first double bond into saturated fatty acyl-CoA substrates (PubMed:15907797, PubMed:18765284). Catalyzes the insertion of a cis double bond at the delta-9 position into fatty acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA (PubMed:15907797, PubMed:18765284). Gives rise to a mixture of 16:1 and 18:1 unsaturated fatty acids (PubMed:15610069). Plays an important role in lipid biosynthesis. Plays an important role in regulating the expression of genes that are involved in lipogenesis and in regulating mitochondrial fatty acid oxidation (By similarity). Plays an important role in body energy homeostasis (By similarity). Contributes to the biosynthesis of membrane phospholipids, cholesterol esters and triglycerides (By similarity).[UniProtKB:P13516][1] [2] [3]
Publication Abstract from PubMed
Stearoyl-coenzyme A desaturase-1 (SCD1) has an important role in lipid metabolism, and SCD1 inhibitors are potential therapeutic agents for the treatment of metabolic diseases and cancers. Here we report the 3.25-A crystal structure of human SCD1 in complex with its substrate, stearoyl-coenzyme A, which defines the new SCD1 dimetal catalytic center and reveals the determinants of substrate binding to provide insights into the catalytic mechanism of desaturation of the stearoyl moiety. The structure also provides a mechanism for localization of SCD1 in the endoplasmic reticulum: human SCD1 folds around a tight hydrophobic core formed from four long alpha-helices that presumably function as an anchor spanning the endoplasmic reticulum membrane. Furthermore, our results provide a framework for the rational design of pharmacological inhibitors targeting the SCD1 enzyme.
Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate.,Wang H, Klein MG, Zou H, Lane W, Snell G, Levin I, Li K, Sang BC Nat Struct Mol Biol. 2015 Jul;22(7):581-5. doi: 10.1038/nsmb.3049. Epub 2015 Jun , 22. PMID:26098317[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Zhang S, Yang Y, Shi Y. Characterization of human SCD2, an oligomeric desaturase with improved stability and enzyme activity by cross-linking in intact cells. Biochem J. 2005 May 15;388(Pt 1):135-42. PMID:15610069 doi:10.1042/BJ20041554
- ↑ Wang J, Yu L, Schmidt RE, Su C, Huang X, Gould K, Cao G. Characterization of HSCD5, a novel human stearoyl-CoA desaturase unique to primates. Biochem Biophys Res Commun. 2005 Jul 8;332(3):735-42. PMID:15907797 doi:10.1016/j.bbrc.2005.05.013
- ↑ Goren MA, Fox BG. Wheat germ cell-free translation, purification, and assembly of a functional human stearoyl-CoA desaturase complex. Protein Expr Purif. 2008 Dec;62(2):171-8. PMID:18765284 doi:10.1016/j.pep.2008.08.002
- ↑ Wang H, Klein MG, Zou H, Lane W, Snell G, Levin I, Li K, Sang BC. Crystal structure of human stearoyl-coenzyme A desaturase in complex with substrate. Nat Struct Mol Biol. 2015 Jul;22(7):581-5. doi: 10.1038/nsmb.3049. Epub 2015 Jun , 22. PMID:26098317 doi:http://dx.doi.org/10.1038/nsmb.3049
|
