6EWT

Solution Structure of Rhabdopeptide NRPS Docking Domain Kj12B-NDD

Summary for 6EWT

• Entry DOI: 10.2210/pdb6ewt/pdb
• NMR Information: BMRB: 34194
• Descriptor: NRPS Kj12B-NDD (1 entity in total)
• Functional Keywords: protein, peptide binding protein
• Biological source: Xenorhabdus stockiae
• Total number of polymer chains: 1
• Total formula weight: 7245.11

Authors

Hacker, C.,Cai, X.,Kegler, C.,Zhao, L.,Weickhmann, A.K.,Bode, H.B.,Woehnert, J. (deposition date: 2017-11-06, release date: 2018-10-31, Last modification date: 2024-06-19)

Primary citation

Hacker, C.,Cai, X.,Kegler, C.,Zhao, L.,Weickhmann, A.K.,Wurm, J.P.,Bode, H.B.,Wohnert, J.
Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS.
Nat Commun, 9:4366-4366, 2018

PubMed Abstract: Several peptides in clinical use are derived from non-ribosomal peptide synthetases (NRPS). In these systems multiple NRPS subunits interact with each other in a specific linear order mediated by specific docking domains (DDs), whose structures are not known yet, to synthesize well-defined peptide products. In contrast to classical NRPSs, single-module NRPS subunits responsible for the generation of rhabdopeptide/xenortide-like peptides (RXPs) can act in different order depending on subunit stoichiometry thereby producing peptide libraries. To define the basis for their unusual interaction patterns, we determine the structures of all N-terminal DDs (DDs) as well as of an DD-DD complex and characterize all putative DD interactions thermodynamically for such a system. Key amino acid residues for DD interactions are identified that upon their exchange change the DD affinity and result in predictable changes in peptide production. Recognition rules for DD interactions are identified that also operate in other megasynthase complexes.

PubMed: 30341296
DOI: 10.1038/s41467-018-06712-1

Experimental method

SOLUTION NMR