title: Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril.
abstract: Angiotensin I-converting enzymes (ACEs) are zinc metallopeptidases that cleave carboxy-terminal dipeptides from short peptide hormones. We have determined the crystal structures of AnCE, a Drosophila homolog of ACE, with and without bound inhibitors to 2.4 A resolution. AnCE contains a large internal channel encompassing the entire protein molecule. This substrate-binding channel is composed of two chambers, reminiscent of a peanut shell. The inhibitor and zinc-binding sites are located in the narrow bottleneck connecting the two chambers. The substrate and inhibitor specificity of AnCE appears to be determined by extensive hydrogen-bonding networks and ionic interactions in the active site channel. The catalytically important zinc ion is coordinated by the conserved Glu395 and histidine residues from a HExxH motif.
authors.affiliation: Department of Biological Science, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, Daejeon, South Korea.
authors.forename: Ho Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Dong Ryeol
authors.initials: DR
authors.lastname: Shin
authors.forename: Ook Joon
authors.initials: OJ
authors.lastname: Yoo
authors.forename: Hayyoung
authors.initials: H
authors.lastname: Lee
authors.forename: Jie-Oh
authors.initials: JO
authors.lastname: Lee
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000378:metabolism*; D000818:Animals; D002216:Captopril / Q000378:metabolism*; D018360:Crystallography, X-Ray; D004330:Drosophila; D017706:Lisinopril / Q000378:metabolism*; D008958:Models, Molecular; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A