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Crystal structure of a peptidyl‐dipeptidase K‐26‐DCP from Actinomycete in complex with its natural inhibitor
Author(s) -
Masuyer Geoffrey,
Cozier Gyles E.,
Kramer Glenna J.,
Bachmann Brian O.,
Acharya K. Ravi
Publication year - 2016
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.13928
Subject(s) - dipeptidase , chemistry , protein data bank (rcsb pdb) , tripeptide , renin–angiotensin system , enzyme , natural product , actinobacteria , biochemistry , stereochemistry , biology , amino acid , 16s ribosomal rna , gene , blood pressure , endocrinology
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 .