3DWB: 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.
PDB ID: 3DWBDownload
MMDB ID: 68136
PDB Deposition Date: 2008/7/22
Updated in MMDB: 2008/11
Experimental Method:
x-ray diffraction
Resolution: 2.38  Å
Source Organism:
Similar Structures:
Biological Unit for 3DWB: monomeric; determined by author and by software (PISA)
Molecular Components in 3DWB
Label Count Molecule
Protein (1 molecule)
Endothelin-converting Enzyme 1(Gene symbol: ECE1)
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB