5ISW: Structure Of The Apo Pcp-e Didomain Of The Gramicidin S Synthetase A

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.
PDB ID: 5ISWDownload
MMDB ID: 140556
PDB Deposition Date: 2016/3/15
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.75  Å
Source Organism:
Similar Structures:
Biological Unit for 5ISW: monomeric; determined by author and by software (PISA)
Molecular Components in 5ISW
Label Count Molecule
Protein (1 molecule)
Gramicidin S Synthase 1
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

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