Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril.
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.
Kim
Ho Min
HM
Department of Biological Science, Korea Advanced Institute of Science and Technology, 373-1 Kusong-dong, Yusong-gu, Daejeon, South Korea.
Shin
Dong Ryeol
DR
Yoo
Ook Joon
OJ
Lee
Hayyoung
H
Lee
Jie-Oh
JO
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
D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D017706:Lisinopril; D007703:Peptidyl-Dipeptidase A