4ca7

Drosophila Angiotensin converting enzyme (AnCE) in complex with a phosphinic tripeptide FIDrosophila Angiotensin converting enzyme (AnCE) in complex with a phosphinic tripeptide FI

Structural highlights 4ca7 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.82Å Ligands: , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACE_DROME May be involved in the specific maturation or degradation of a number of bioactive peptides. May play a role in the contractions of the heart, gut and testes, and in spermatid differentiation. Publication Abstract from PubMed Human somatic angiotensin-I converting enzyme (ACE) is a zinc-dependent dipeptidyl carboxypeptidase and a central component of the renin angiotensin-aldosterone system (RAAS). Its involvement in the modulation of physiological actions of peptide hormones has positioned ACE as an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the crystal structures of the two catalytic domains of human ACE (N- and C-) in complex with FI, the S enantiomer of the phosphinic ACE/ECE-1 (endothelin converting enzyme) dual inhibitor FII, to a resolution of 1.91A and 1.85 A, respectively. In addition, we have determined the structure of AnCE (an ACE homologue from Drosophila melanogaster) in complex with both isomers. The inhibitor FI (S configuration) can adapt to the active site of ACE catalytic domains and shows key differences in its binding mechanism mostly through the reorientation of the isoxazole phenyl side group at the P1 ' position, compared to FII (R configuration). Differences in binding are also observed between FI and FII in complex with AnCE. Thus, the new structures of the ACE-inhibitor complexes presented here provide useful information for further exploration of ACE inhibitor pharmacophores involving phosphinic peptides and illustrate the role of chirality in enhancing drug specificity. This article is protected by copyright. All rights reserved. Crystal structures of highly specific phosphinic tripeptide enantiomers in complex with the angiotensin-I converting enzyme.,Masuyer G, Akif M, Czarny B, Beau F, Schwager SL, Sturrock ED, Isaac RE, Dive V, Acharya KR FEBS J. 2013 Nov 29. doi: 10.1111/febs.12660. PMID:24289879 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Angiotensin-Converting Enzyme 3D structures

spinqualitylabelsall models 4ca7, resolution 1.82Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image