title: Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster.
abstract: Angiotensin-I converting enzyme (ACE, a zinc dependent dipeptidyl carboxypeptidase) is a major target of drugs due to its role in the modulation of blood pressure and cardiovascular disorders. Here we present a crystal structure of AnCE (an ACE homologue from Drosophila melanogaster with a single enzymatic domain) in complex with a natural product-phosphonotripeptide, K-26 at 1.96A resolution. The inhibitor binds exclusively in the S(1) and S(2) binding pockets of AnCE (coordinating the zinc ion) through ionic and hydrogen bond interactions. A detailed structural comparison of AnCE.K-26 complex with individual domains of human somatic ACE provides useful information for further exploration of ACE inhibitor pharmacophores involving phosphonic acids.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Mohd
authors.initials: M
authors.lastname: Akif
authors.forename: Ioanna
authors.initials: I
authors.lastname: Ntai
authors.forename: Edward D
authors.initials: ED
authors.lastname: Sturrock
authors.forename: R Elwyn
authors.initials: RE
authors.lastname: Isaac
authors.forename: Brian O
authors.initials: BO
authors.lastname: Bachmann
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D018360:Crystallography, X-Ray; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D004331:Drosophila melanogaster; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry; D017434:Protein Structure, Tertiary
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D029721:Drosophila Proteins; D009842:Oligopeptides; C508953:tripeptide K-26; C104431:Ance protein, Drosophila; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A; D008666:Metalloendopeptidases