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| | ==Hydroxylase domain of scs7p== | | ==Hydroxylase domain of scs7p== |
| - | <StructureSection load='4zr1' size='340' side='right' caption='[[4zr1]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='4zr1' size='340' side='right'caption='[[4zr1]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4zr1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZR1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZR1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4zr1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZR1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ZR1 FirstGlance]. <br> |
| | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=TRD:TRIDECANE'>TRD</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"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=TRD:TRIDECANE'>TRD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=4zr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zr1 OCA], [http://pdbe.org/4zr1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zr1 RCSB], [http://www.ebi.ac.uk/pdbsum/4zr1 PDBsum]</span></td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SCS7, FAH1, YMR272C, YM8156.14C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=4zr1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zr1 OCA], [http://pdbe.org/4zr1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4zr1 RCSB], [http://www.ebi.ac.uk/pdbsum/4zr1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4zr1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Baker's yeast]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Koszelak-Rosenblum, M]] | | [[Category: Koszelak-Rosenblum, M]] |
| | [[Category: MPSBC, Membrane Protein Structural Biology Consortium]] | | [[Category: MPSBC, Membrane Protein Structural Biology Consortium]] |
| Structural highlights
4zr1 is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , |
| Gene: | SCS7, FAH1, YMR272C, YM8156.14C (Baker's yeast) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SCS7_YEAST] Ceramide hydroxylase involved in the alpha-hydroxylation of sphingolipid-associated very long chain fatty acids. Hydroxylates the very long chain fatty acid of ceramides at C2 and C3.[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
Neuronal electrical impulse propagation is facilitated by the myelin sheath, a compact membrane surrounding the axon. The myelin sheath is highly enriched in galactosylceramide (GalCer) and its sulfated derivative sulfatide. Over 50% of GalCer and sulfatide in myelin is hydroxylated by the integral membrane enzyme fatty acid 2-hydroxylase (FA2H). GalCer hydroxylation contributes to the compact nature of the myelin membrane and mutations in FA2H result in debilitating leukodystrophies and spastic paraparesis. We report here the 2.6 A crystal structure of sphingolipid alpha-hydroxylase (Scs7p), a yeast homolog of FA2H. The Scs7p core is comprised of a helical catalytic cap domain that sits atop four transmembrane helices that anchor the enzyme in the endoplasmic reticulum. The structure contains two zinc atoms coordinated by the side chains of 10 highly conserved histidines within a dimetal center located near the plane of the cytosolic membrane. We used a yeast genetic approach to confirm the important role of the dimetal-binding histidines in catalysis and identified Tyr-322 and Asp-323 as critical determinants involved in the hydroxylase reaction. Examination of the Scs7p structure, coupled with molecular dynamics simulations, allowed for the generation of a model of ceramide binding to Scs7p. Comparison of the Scs7p structure and substrate-binding model to the structure of steroyl-CoA desaturase revealed significant differences in the architectures of the catalytic cap domain and location of the dimetal centers with respect to the membrane. These observations provide insight into the different mechanisms of substrate binding and recognition of substrates by the hydroxylase and desaturase enzymes.
The crystal structure of an integral membrane fatty acid alpha-hydroxylase.,Zhu G, Koszelak-Rosenblum M, Connelly SM, Dumont ME, Malkowski MG J Biol Chem. 2015 Oct 28. pii: jbc.M115.680124. PMID:26515067[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Swain E, Baudry K, Stukey J, McDonough V, Germann M, Nickels JT Jr. Sterol-dependent regulation of sphingolipid metabolism in Saccharomyces cerevisiae. J Biol Chem. 2002 Jul 19;277(29):26177-84. Epub 2002 May 10. PMID:12006573 doi:http://dx.doi.org/10.1074/jbc.M204115200
- ↑ Guan XL, Wenk MR. Mass spectrometry-based profiling of phospholipids and sphingolipids in extracts from Saccharomyces cerevisiae. Yeast. 2006 Apr 30;23(6):465-77. PMID:16652392 doi:http://dx.doi.org/10.1002/yea.1362
- ↑ Bosson R, Guillas I, Vionnet C, Roubaty C, Conzelmann A. Incorporation of ceramides into Saccharomyces cerevisiae glycosylphosphatidylinositol-anchored proteins can be monitored in vitro. Eukaryot Cell. 2009 Mar;8(3):306-14. doi: 10.1128/EC.00257-08. Epub 2008 Dec 12. PMID:19074599 doi:http://dx.doi.org/10.1128/EC.00257-08
- ↑ Mitchell AG, Martin CE. Fah1p, a Saccharomyces cerevisiae cytochrome b5 fusion protein, and its Arabidopsis thaliana homolog that lacks the cytochrome b5 domain both function in the alpha-hydroxylation of sphingolipid-associated very long chain fatty acids. J Biol Chem. 1997 Nov 7;272(45):28281-8. PMID:9353282
- ↑ Haak D, Gable K, Beeler T, Dunn T. Hydroxylation of Saccharomyces cerevisiae ceramides requires Sur2p and Scs7p. J Biol Chem. 1997 Nov 21;272(47):29704-10. PMID:9368039
- ↑ Dunn TM, Haak D, Monaghan E, Beeler TJ. Synthesis of monohydroxylated inositolphosphorylceramide (IPC-C) in Saccharomyces cerevisiae requires Scs7p, a protein with both a cytochrome b5-like domain and a hydroxylase/desaturase domain. Yeast. 1998 Mar 15;14(4):311-21. PMID:9559540 doi:<311::AID-YEA220>3.0.CO;2-B http://dx.doi.org/10.1002/(SICI)1097-0061(19980315)14:4<311::AID-YEA220>3.0.CO;2-B
- ↑ Zhu G, Koszelak-Rosenblum M, Connelly SM, Dumont ME, Malkowski MG. The crystal structure of an integral membrane fatty acid alpha-hydroxylase. J Biol Chem. 2015 Oct 28. pii: jbc.M115.680124. PMID:26515067 doi:http://dx.doi.org/10.1074/jbc.M115.680124
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