Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster

Mohd Akif, Ioanna Ntai, Edward D. Sturrock, R. Elwyn Isaac, Brian O. Bachmann, K. Ravi Acharya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide, K-26 at 1.96Å resolution. The inhibitor binds exclusively in the S1 and S2 binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE·K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids.

Original languageEnglish (US)
Pages (from-to)532-536
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume398
Issue number3
DOIs
StatePublished - Jul 2010

Keywords

  • Angiotensin converting enzyme
  • Drosophila melanogaster
  • Inhibitor binding
  • X-ray crystallography
  • Zinc metallopeptidase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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