5ISX

Interdomain and Intermodule Organization in Epimerization Domain Containing Nonribosomal Peptide Synthetases.

(2016) ACS Chem Biol 11: 2293-2303

• PubMed: 27294598 Search on PubMed
• DOI: https://doi.org/10.1021/acschembio.6b00332
• Primary Citation of Related Structures:  
  5ISW, 5ISX


• PubMed Abstract: 
  

  Nonribosomal peptide synthetases are large, complex multidomain enzymes responsible for the biosynthesis of a wide range of peptidic natural products. Inherent to synthetase chemistry is the thioester templated mechanism that relies on protein/protein interactions and interdomain dynamics. Several questions related to structure and mechanism remain to be addressed, including the incorporation of accessory domains and intermodule interactions. The inclusion of nonproteinogenic d-amino acids into peptide frameworks is a common and important modification for bioactive nonribosomal peptides. Epimerization domains, embedded in nonribosomal peptide synthetases assembly lines, catalyze the l- to d-amino acid conversion. Here we report the structure of the epimerization domain/peptidyl carrier protein didomain construct from the first module of the cyclic peptide antibiotic gramicidin synthetase. Both holo (phosphopantethiene post-translationally modified) and apo structures were determined, each representing catalytically relevant conformations of the two domains. The structures provide insight into domain-domain recognition, substrate delivery during the assembly line process, in addition to the structural organization of homologous condensation domains, canonical players in all synthetase modules.

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Organizational Affiliation: 

Department of Chemistry, University of Florida , P.O. Box 117200, Gainesville, Florida 32611, United States.