Crystal structure of a peptidyl-dipeptidase K-26-DCP from Actinomycete in complex with its natural inhibitor

FEBS J. 2016 Dec;283(23):4357-4369. doi: 10.1111/febs.13928. Epub 2016 Nov 6.

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.

Database: Structural data are available in the PDB under the accession numbers 5L43 and 5L44.

Keywords: K-26 tripeptide; angiotensin-I-converting enzyme; dipeptidyl carboxypeptidase; metalloprotease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / enzymology*
  • Actinobacteria / genetics
  • Amino Acid Sequence
  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Crystallography, X-Ray
  • Databases, Protein
  • Endopeptidases / chemistry*
  • Endopeptidases / genetics
  • Endopeptidases / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Humans
  • Models, Molecular
  • Oligopeptides / chemistry*
  • Oligopeptides / metabolism
  • Peptidyl-Dipeptidase A / chemistry
  • Peptidyl-Dipeptidase A / metabolism
  • Protein Binding
  • Protein Domains
  • Sequence Homology, Amino Acid

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Bacterial Proteins
  • Enzyme Inhibitors
  • Oligopeptides
  • tripeptide K-26
  • Endopeptidases
  • dipeptidyl carboxypeptidase
  • Peptidyl-Dipeptidase A