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 language | English (US) |
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Pages (from-to) | 532-536 |
Number of pages | 5 |
Journal | Biochemical and Biophysical Research Communications |
Volume | 398 |
Issue number | 3 |
DOIs | |
State | Published - 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