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Structural characterization of angiotensin I‐converting enzyme in complex with a selenium analogue of captopril
Author(s) -
Akif Mohd,
Masuyer Geoffrey,
Schwager Sylva L. U.,
Bhuyan Bhaskar J.,
Mugesh Govindasamy,
Isaac R. Elwyn,
Sturrock Edward D.,
Acharya K. Ravi
Publication year - 2011
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2011.08276.x
Subject(s) - captopril , chemistry , ace inhibitor , selenium , angiotensin converting enzyme , pharmacophore , enzyme , renin–angiotensin system , renin inhibitor , selenocysteine , biochemistry , pharmacology , endocrinology , medicine , cysteine , organic chemistry , blood pressure
Human somatic angiotensin I‐converting enzyme (ACE), a zinc‐dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin–angiotensin aldosterone system. It is a well‐known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [ Org. Biomol. Chem. (2011) 9 , 1356–1365], it was shown that the selenium analogues of captopril (a well‐known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite‐mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 Å resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein–selenolate interaction. These new structures of tACE–SeCap and AnCE–SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium‐based ACE inhibitor pharmacophores with significant antioxidant activity. Database
Structural data for the two SeCap complexes with ACE and AnCE have been deposited with the RCSB Protein Data Bank under the codes 2YDM and 3ZQZ , respectively.