Structure-based redesign of docking domain interactions modulates the product 
spectrum of a rhabdopeptide-synthesizing NRPS

Hacker, Carolin; Cai, Xiaofeng; Kegler, Carsten; Zhao, Lei; Weickhmann, A. Katharina; Wurm, Jan Philip; Bode, Helge B.; Woehnert, Jens

doi:10.1038/s41467-018-06712-1

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS

MPS-Authors

There are no MPG-Authors in the publication available

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Hacker, C., Cai, X., Kegler, C., Zhao, L., Weickhmann, A. K., Wurm, J. P., et al. (2018). Structure-based redesign of docking domain interactions modulates the product spectrum of a rhabdopeptide-synthesizing NRPS. NATURE COMMUNICATIONS, 9: 4366. doi:10.1038/s41467-018-06712-1.

Cite as: https://hdl.handle.net/21.11116/0000-000A-05D6-F

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 ((N)DDs) as well as of an (DD)-D-N-(DD)-D-C 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.