Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
Biochem Biophys Res Commun. 2010 Jul 30;398(3):532-6. doi: 10.1016/j.bbrc.2010.06.113. Epub 2010 Jul 1.
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 1.96A resolution. The inhibitor binds exclusively in the S(1) and S(2) 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.
血管紧张素转化酶（ACE，一种锌依赖性二肽羧肽酶）是药物的主要靶点，因为它在调节血压和心血管疾病方面发挥着作用。在这里，我们展示了一个来自黑腹果蝇的 ACE 同源物（具有单个酶结构域）与天然产物膦三肽 K-26 的复合物的晶体结构，分辨率为 1.96A。抑制剂通过离子和氢键相互作用，专门结合到 AnCE（协调锌离子）的 S(1)和 S(2)结合口袋中。AnCE.K-26 复合物与人类体细胞 ACE 的各个结构域的详细结构比较，为进一步探索涉及膦酸的 ACE 抑制剂药效团提供了有用的信息。
