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3dwb
From Proteopedia
| 3dwb, resolution 2.38Å () | |||||
|---|---|---|---|---|---|
| Sites: | , and | ||||
| Ligands: | , , | ||||
| Gene: | ECE1 (Homo sapiens) | ||||
| Activity: | Endothelin-converting enzyme 1, with EC number 3.4.24.71 | ||||
| Related: | 1dmt | ||||
| |||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||
| Coordinates: | save as pdb, mmCIF, xml | ||||
Contents |
structure of human ECE-1 complexed with phosphoramidon
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. 2008 Nov 1. PMID:18992253
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Disease
Known disease associated with this structure: Hirschsprung disease, cardiac defects, and autonomic dysfunction OMIM:[600423], Hypertension, essential, susceptibility to OMIM:[600423]
About this Structure
3DWB is a 1 chain structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- 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
Page seeded by OCA on Wed Jun 24 20:16:17 2009
Categories: Endothelin-converting enzyme 1 | Homo sapiens | Oefner, C. | Alternative splicing | Disease mutation | Glycoprotein | Hirschsprung disease | Hydrolase | Mch ece h 25a1 lt1 pdb | Membrane | Metal-binding | Metalloprotease | Phosphoprotein | Polymorphism | Protease | Protein | Signal-anchor | Transmembrane | Zinc
