3dwb

From Proteopedia

(Difference between revisions)

Current revision

structure of human ECE-1 complexed with phosphoramidon

Structural highlights

3dwb is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.38Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3dwb"

Categories: Homo sapiens | Large Structures | Oefner C

@@ Line 3: / Line 3: @@
 <StructureSection load='3dwb' size='340' side='right'caption='[[3dwb]], [[Resolution|resolution]] 2.38&Aring;' scene=''>
 == 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]] 2.38&#8491;</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>
 </table>
 == 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 ==
-[[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 19: / Line 17: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dw/3dwb_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 37: / Line 35: @@
 __TOC__
 </StructureSection>
-[[Category: Endothelin-converting enzyme 1]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
 [[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]]

3dwb

From Proteopedia

Current revision

structure of human ECE-1 complexed with phosphoramidon

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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