Captopril [2]

Mechanism of action

Captopril is the smallest orally active tight-binding peptide analogue inhibitor of angiotensin converting enzyme (ACE). The thiol-coordinating group of the inhibitor makes a direct interaction with the catalytic Zn(2+) ion (distance, 2.15 Å) (Figure 3 A). Additionally, the captopril molecule is held by eight H-bonds, including three with water molecules. The central carbonyl oxygen positioned between the thiol and the terminal proline moiety of captopril is anchored by two strong H-bonds with His337 and His497. One of the oxygen atoms from captopril's proline carboxylate group is held by interactions with side-chains of residues Gln265, Lys495 and Tyr504. The other oxygen of the proline is held indirectly by water-molecule-mediated interactions with Asn261 and Glu150. A network of water molecules makes indirect interactions between the carboxylate oxygen and with Arg356, Asp360 and Gln361.

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Model options CPK > Binding site H-bonds, Figure 3 A view > Drug molecule Show within 8 Å

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Crystal structure of Drosophila melanogaster angiotensin-converting enzyme in complex with captopril [PDB structure code 2X8Z]
M. Akif, D. Georgiadis, A. Mahajan, V. Dive, E. D. Sturrock, R. E. Isaac and K. R. Acharya, J. Mol. Biol., 2010, 400, 502–517 (doi:10.1016/j.jmb.2010.05.024).