کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1931577 | 1050557 | 2010 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster](/preview/png/1931577.png)
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 1.96 Å 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.
Research highlights
► This is first structure of AnCE (an ACE homologue) in complex with a natural peptide inhibitor K-26
► K-26 binds exclusively at the non-prime binding pockets in the active site of AnCE
► High resolution crystal structure of AnCE·K-26 complex
Journal: Biochemical and Biophysical Research Communications - Volume 398, Issue 3, 30 July 2010, Pages 532–536