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| | <StructureSection load='6ohu' size='340' side='right'caption='[[6ohu]], [[Resolution|resolution]] 3.53Å' scene=''> | | <StructureSection load='6ohu' size='340' side='right'caption='[[6ohu]], [[Resolution|resolution]] 3.53Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ohu]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OHU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6OHU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ohu]] is a 3 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=6OHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OHU FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CTX:(Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE'>CTX</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.526Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cholestenol_Delta-isomerase Cholestenol Delta-isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.3.5 5.3.3.5] </span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTX:(Z)-2-[4-(1,2)-DIPHENYL-1-BUTENYL)-PHENOXY]-N,N-DIMETHYLETHANAMINE'>CTX</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=6ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ohu OCA], [http://pdbe.org/6ohu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ohu RCSB], [http://www.ebi.ac.uk/pdbsum/6ohu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ohu ProSAT]</span></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=6ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ohu OCA], [https://pdbe.org/6ohu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ohu RCSB], [https://www.ebi.ac.uk/pdbsum/6ohu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ohu ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN] MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN]] Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.<ref>PMID:12760743</ref> <ref>PMID:8798407</ref> <ref>PMID:9894009</ref> | + | [https://www.uniprot.org/uniprot/EBP_HUMAN EBP_HUMAN] Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.<ref>PMID:12760743</ref> <ref>PMID:8798407</ref> <ref>PMID:9894009</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Cholestenol Delta-isomerase]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Long, T]] | + | [[Category: Long T]] |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Isomerase-inhibitor complex]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Disease
EBP_HUMAN MEND syndrome;X-linked dominant chondrodysplasia punctata. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
EBP_HUMAN Catalyzes the conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.[1] [2] [3]
Publication Abstract from PubMed
3-beta-hydroxysteroid-Delta(8), Delta(7)-isomerase, known as Emopamil-Binding Protein (EBP), is an endoplasmic reticulum membrane protein involved in cholesterol biosynthesis, autophagy, oligodendrocyte formation. The mutation on EBP can cause Conradi-Hunermann syndrome, an inborn error. Interestingly, EBP binds an abundance of structurally diverse pharmacologically active compounds, causing drug resistance. Here, we report two crystal structures of human EBP, one in complex with the anti-breast cancer drug tamoxifen and the other in complex with the cholesterol biosynthesis inhibitor U18666A. EBP adopts an unreported fold involving five transmembrane-helices (TMs) that creates a membrane cavity presenting a pharmacological binding site that accommodates multiple different ligands. The compounds exploit their positively-charged amine group to mimic the carbocationic sterol intermediate. Mutagenesis studies on specific residues abolish the isomerase activity and decrease the multidrug binding capacity. This work reveals the catalytic mechanism of EBP-mediated isomerization in cholesterol biosynthesis and how this protein may act as a multi-drug binder.
Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition.,Long T, Hassan A, Thompson BM, McDonald JG, Wang J, Li X Nat Commun. 2019 Jun 5;10(1):2452. doi: 10.1038/s41467-019-10279-w. PMID:31165728[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Moebius FF, Fitzky BU, Wietzorrek G, Haidekker A, Eder A, Glossmann H. Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol delta8-delta7 isomerase activity. Biochem J. 2003 Aug 15;374(Pt 1):229-37. PMID:12760743 doi:http://dx.doi.org/10.1042/BJ20030465
- ↑ Silve S, Dupuy PH, Labit-Lebouteiller C, Kaghad M, Chalon P, Rahier A, Taton M, Lupker J, Shire D, Loison G. Emopamil-binding protein, a mammalian protein that binds a series of structurally diverse neuroprotective agents, exhibits delta8-delta7 sterol isomerase activity in yeast. J Biol Chem. 1996 Sep 13;271(37):22434-40. PMID:8798407
- ↑ Moebius FF, Soellner KE, Fiechtner B, Huck CW, Bonn G, Glossmann H. Histidine77, glutamic acid81, glutamic acid123, threonine126, asparagine194, and tryptophan197 of the human emopamil binding protein are required for in vivo sterol delta 8-delta 7 isomerization. Biochemistry. 1999 Jan 19;38(3):1119-27. PMID:9894009 doi:http://dx.doi.org/10.1021/bi981804i
- ↑ Long T, Hassan A, Thompson BM, McDonald JG, Wang J, Li X. Structural basis for human sterol isomerase in cholesterol biosynthesis and multidrug recognition. Nat Commun. 2019 Jun 5;10(1):2452. doi: 10.1038/s41467-019-10279-w. PMID:31165728 doi:http://dx.doi.org/10.1038/s41467-019-10279-w
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