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| | <StructureSection load='3dwb' size='340' side='right'caption='[[3dwb]], [[Resolution|resolution]] 2.38Å' scene=''> | | <StructureSection load='3dwb' size='340' side='right'caption='[[3dwb]], [[Resolution|resolution]] 2.38Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3dwb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3DWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DWB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3dwb]] 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=3DWB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DWB FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5HD:5-(2-HYDROXYETHYL)NONANE-1,9-DIOL'>5HD</scene>, <scene name='pdbligand=RDF:N-ALPHA-L-RHAMNOPYRANOSYLOXY(HYDROXYPHOSPHINYL)-L-LEUCYL-L-TRYPTOPHAN'>RDF</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.38Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1dmt|1dmt]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5HD:5-(2-HYDROXYETHYL)NONANE-1,9-DIOL'>5HD</scene>, <scene name='pdbligand=RDF:N-ALPHA-L-RHAMNOPYRANOSYLOXY(HYDROXYPHOSPHINYL)-L-LEUCYL-L-TRYPTOPHAN'>RDF</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">ECE1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Endothelin-converting_enzyme_1 Endothelin-converting enzyme 1], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.24.71 3.4.24.71] </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=3dwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dwb OCA], [https://pdbe.org/3dwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dwb RCSB], [https://www.ebi.ac.uk/pdbsum/3dwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dwb 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=3dwb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dwb OCA], [https://pdbe.org/3dwb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dwb RCSB], [https://www.ebi.ac.uk/pdbsum/3dwb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dwb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/ECE1_HUMAN ECE1_HUMAN]] Defects in ECE1 are a cause of Hirschsprung disease cardiac defects and autonomic dysfunction (HSCRCDAD) [MIM:[https://omim.org/entry/613870 613870]]. It is a form of Hirschsprung disease with skip-lesions defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction.<ref>PMID:9915973</ref>
| + | [https://www.uniprot.org/uniprot/ECE1_HUMAN ECE1_HUMAN] Defects in ECE1 are a cause of Hirschsprung disease cardiac defects and autonomic dysfunction (HSCRCDAD) [MIM:[https://omim.org/entry/613870 613870]. It is a form of Hirschsprung disease with skip-lesions defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction.<ref>PMID:9915973</ref> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ECE1_HUMAN ECE1_HUMAN]] Converts big endothelin-1 to endothelin-1.<ref>PMID:9396733</ref>
| + | [https://www.uniprot.org/uniprot/ECE1_HUMAN ECE1_HUMAN] Converts big endothelin-1 to endothelin-1.<ref>PMID:9396733</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Endothelin-converting enzyme 1]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Oefner, C]] | + | [[Category: Oefner C]] |
| - | [[Category: Disease mutation]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Hirschsprung disease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Mch_ece_h_25a1_lt1 pdb]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Metal-binding]]
| + | |
| - | [[Category: Metalloprotease]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protease]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Signal-anchor]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Disease
ECE1_HUMAN Defects in ECE1 are a cause of Hirschsprung disease cardiac defects and autonomic dysfunction (HSCRCDAD) [MIM:613870. It is a form of Hirschsprung disease with skip-lesions defects, craniofacial abnormalities and other dysmorphic features, and autonomic dysfunction.[1]
Function
ECE1_HUMAN Converts big endothelin-1 to endothelin-1.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Endothelin-converting enzyme I (ECE-1) is a mammalian type II integral membrane zinc-containing endopeptidase. ECE-1 catalyzes the final step in the biosynthesis of endothelins in a rate-limiting fashion, through post-translational conversion of the biologically inactive big endothelins. Endothelin-1 overproduction has been implicated in a heterogeneous list of diseases including systemic and pulmonary hypertension, stroke and asthma, cardiac and renal failure. Therefore, ECE-1 is a prime therapeutic target for the regulation of endothelin-1 production in vivo and there is considerable interest in selective inhibitors of this enzyme. Here, we present the crystal structure of the extracellular domain (residues 90-770) of human ECE-1 (C428S) with the generic metalloprotease inhibitor phosphoramidon determined at 2.38 A resolution. The structure is closely related to that of human NEP, providing essential information for a detailed understanding of ligand-binding, specificity determinants as well as selectivity criteria. Selective inhibitors of ECE-1s should have beneficial effects for the treatment of diseases in which an overproduction of ETs plays a pathogenic role.
Structure of human endothelin-converting enzyme I complexed with phosphoramidon.,Schulz H, Dale GE, Karimi-Nejad Y, Oefner C J Mol Biol. 2009 Jan 9;385(1):178-87. Epub 2008 Nov 1. PMID:18992253[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Hofstra RM, Valdenaire O, Arch E, Osinga J, Kroes H, Loffler BM, Hamosh A, Meijers C, Buys CH. A loss-of-function mutation in the endothelin-converting enzyme 1 (ECE-1) associated with Hirschsprung disease, cardiac defects, and autonomic dysfunction. Am J Hum Genet. 1999 Jan;64(1):304-8. PMID:9915973 doi:10.1086/302184
- ↑ Schweizer A, Valdenaire O, Nelbock P, Deuschle U, Dumas Milne Edwards JB, Stumpf JG, Loffler BM. Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. Biochem J. 1997 Dec 15;328 ( Pt 3):871-7. PMID:9396733
- ↑ Schulz H, Dale GE, Karimi-Nejad Y, Oefner C. Structure of human endothelin-converting enzyme I complexed with phosphoramidon. J Mol Biol. 2009 Jan 9;385(1):178-87. Epub 2008 Nov 1. PMID:18992253 doi:10.1016/j.jmb.2008.10.052
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