3ZQZ

CRYSTAL STRUCTURE OF ANCE IN COMPLEX WITH A SELENIUM ANALOGUE OF CAPTOPRIL

Summary for 3ZQZ

• Entry DOI: 10.2210/pdb3zqz/pdb
• Related: 1J36 1J37 1J38 2X8Y 2X8Z 2X90 2X91 2X92 2X93 2X94 2X95 2X96 2X97 2XHM
• Descriptor: ANGIOTENSIN-CONVERTING ENZYME, beta-D-mannopyranose-(1-6)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (6 entities in total)
• Functional Keywords: hydrolase, inhibitor design
• Biological source: DROSOPHILA MELANOGASTER
• Cellular location: Secreted, extracellular space: Q10714
• Total number of polymer chains: 1
• Total formula weight: 70995.55

Authors

Akif, M.,Masuyer, G.,Schwager, S.L.U.,Bhuyan, B.J.,Mugesh, G.,Isaac, R.E.,Sturrock, E.D.,Acharya, K.R. (deposition date: 2011-06-13, release date: 2011-09-14, Last modification date: 2024-10-23)

Primary citation

Akif, M.,Masuyer, G.,Schwager, S.L.,Bhuyan, B.J.,Mugesh, G.,Isaac, R.E.,Sturrock, E.D.,Acharya, K.R.
Structural Characterization of Angiotensin I- Converting Enzyme in Complex with a Selenium Analogue of Captopril.
FEBS J., 278:3644-, 2011

PubMed Abstract: 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.

PubMed: 21810173
DOI: 10.1111/J.1742-4658.2011.08276.X

Experimental method

X-RAY DIFFRACTION (2.35 Å)