title: Crystal structure of a peptidyl-dipeptidase K-26-DCP from Actinomycete in complex with its natural inhibitor.
abstract: Several soil-derived Actinobacteria produce secondary metabolites that are proven specific and potent inhibitors of the human angiotensin-I-converting enzyme (ACE), a key target for the modulation of hypertension through its role in the renin-angiotensin-aldosterone system. K-26-DCP is a zinc dipeptidyl carboxypeptidase (DCP) produced by Astrosporangium hypotensionis, and an ancestral homologue of ACE. Here we report the high-resolution crystal structures of K-26-DCP and of its complex with the natural microbial tripeptide product K-26. The experimental results provide the structural basis for better understanding the specificity of K-26 for human ACE over bacterial DCPs.
  
  
  
  Structural data are available in the PDB under the accession numbers 5L43 and 5L44.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Masuyer
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: Gyles E
authors.initials: GE
authors.lastname: Cozier
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
authors.forename: Glenna J
authors.initials: GJ
authors.lastname: Kramer
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, TN, USA.
authors.forename: Brian O
authors.initials: BO
authors.lastname: Bachmann
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: K Ravi
authors.initials: KR
authors.lastname: Acharya
mesh_terms: D039903:Actinobacteria / Q000201:enzymology* / Q000235:genetics; D000595:Amino Acid Sequence; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D030562:Databases, Protein; D010450:Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D017386:Sequence Homology, Amino Acid
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D009842:Oligopeptides; C508953:tripeptide K-26; D010450:Endopeptidases; C020071:dipeptidyl carboxypeptidase; D007703:Peptidyl-Dipeptidase A
keywords: K-26 tripeptide; angiotensin-I-converting enzyme; dipeptidyl carboxypeptidase; metalloprotease