5ISW

Structure of the apo PCP-E didomain of the gramicidin S synthetase A

Summary for 5ISW

• Entry DOI: 10.2210/pdb5isw/pdb
• Related: 5ISX
• Descriptor: Gramicidin S synthase 1, GLYCEROL (3 entities in total)
• Functional Keywords: epimerization domain, nrps, gramicidin s synthetase, isomerase
• Biological source: Brevibacillus brevis
• Total number of polymer chains: 1
• Total formula weight: 67330.80

Authors

Chen, W.-H.,Li, K.,Bruner, S.D. (deposition date: 2016-03-15, release date: 2016-06-29, Last modification date: 2024-03-06)

Primary citation

Chen, W.H.,Li, K.,Guntaka, N.S.,Bruner, S.D.
Interdomain and Intermodule Organization in Epimerization Domain Containing Nonribosomal Peptide Synthetases.
Acs Chem.Biol., 11:2293-2303, 2016

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.

PubMed: 27294598
DOI: 10.1021/acschembio.6b00332

Experimental method

X-RAY DIFFRACTION (1.75 Å)