A three-dimensional model of endothelin-converting enzyme (ECE) based on the X-ray structure of neutral endopeptidase 24.11 (NEP)

Protein Eng. 2001 May;14(5):337-41. doi: 10.1093/protein/14.5.337.


Endothelin-converting enzyme 1 (ECE-1, EC is a zinc-dependent type II mammalian membrane protein comprising the active site in the ectodomain. It exists in multiple splice variants that all catalyze the last and rate-limiting step in the activation of preproendothelin to the highly potent vasoconstrictor endothelin. There is high interest in finding small and potent inhibitors for this enzyme that could be used in numerous indications, e.g. hypertension. Since there is no structural information available for this important enzyme, we built a model of the complete ectodomain using the recently solved structure of human NEP as template. The naturally derived metalloproteinase inhibitor phosphoramidon was docked in the active site of this model and comparisons with the respective NEP complex were made.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Aspartic Acid Endopeptidases / antagonists & inhibitors
  • Aspartic Acid Endopeptidases / chemistry*
  • Aspartic Acid Endopeptidases / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Endothelin-Converting Enzymes
  • Glycopeptides / metabolism
  • Humans
  • Metalloendopeptidases / antagonists & inhibitors
  • Metalloendopeptidases / chemistry
  • Metalloendopeptidases / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Neprilysin / chemistry*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Substrate Specificity


  • Glycopeptides
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Neprilysin
  • ECE1 protein, human
  • Endothelin-Converting Enzymes
  • phosphoramidon