2YDM

Structural characterization of angiotensin-I converting enzyme in complex with a selenium analogue of captopril

Summary for 2YDM

• Entry DOI: 10.2210/pdb2ydm/pdb
• Related: 1O86 1O8A 1UZE 1UZF 2C6F 2C6N 2IUL 2IUX 2XY9 2XYD
• Descriptor: ANGIOTENSIN CONVERTING ENZYME, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ZINC ION, ... (7 entities in total)
• Functional Keywords: hydrolase, antihypertensive agents
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Angiotensin-converting enzyme, soluble form: Secreted. Cell membrane; Single-pass type I membrane protein: P12821
• Total number of polymer chains: 1
• Total formula weight: 69306.16

Authors

Akif, M.,Masuyer, G.,Schwager, S.L.U.,Bhuyan, B.J.,Mugesh, G.,Sturrock, E.D.,Acharya, K.R. (deposition date: 2011-03-22, release date: 2011-09-14, Last modification date: 2023-12-20)

Primary citation

Akif, M.,Masuyer, G.,Schwager, S.L.U.,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 (2.44 Å)