3DWB

structure of human ECE-1 complexed with phosphoramidon

Summary for 3DWB

• Entry DOI: 10.2210/pdb3dwb/pdb
• Related: 1DMT
• Related PRD ID: PRD_000638
• Descriptor: Endothelin-converting enzyme 1, ZINC ION, 5-(2-hydroxyethyl)nonane-1,9-diol, ... (5 entities in total)
• Functional Keywords: protein, disease mutation, glycoprotein, hirschsprung disease, hydrolase, membrane, metal-binding, metalloprotease, phosphoprotein, protease, signal-anchor, transmembrane, mch_ece_h_25a1_lt1.pdb
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane; Single-pass type II membrane protein: P42892
• Total number of polymer chains: 1
• Total formula weight: 77276.17

Authors

Oefner, C. (deposition date: 2008-07-22, release date: 2008-11-25, Last modification date: 2024-03-20)

Primary citation

Schulz, H.,Dale, G.E.,Karimi-Nejad, Y.,Oefner, C.
Structure of human endothelin-converting enzyme I complexed with phosphoramidon
J.Mol.Biol., 385:178-187, 2009

PubMed Abstract: 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.

PubMed: 18992253
DOI: 10.1016/j.jmb.2008.10.052

Experimental method

X-RAY DIFFRACTION (2.38 Å)