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Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster |
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| Authors: | Mohd Akif Edward D Sturrock Brian O Bachmann |
| Institution: | a Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK b University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA c Division of Medical Biochemistry and Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa d Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, Clarendon Way, University of Leeds, Leeds LS2 9JT, UK e Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA |
| 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 1.96 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. |
| Keywords: | Angiotensin converting enzyme Zinc metallopeptidase X-ray crystallography Inhibitor binding Drosophila melanogaster |
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