Context-dependent activity of A domains in the tyrocidine synthetase View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Anna Degen, Florian Mayerthaler, Henning D. Mootz, Barbara Di Ventura

ABSTRACT

Non-ribosomal peptide synthetases (NRPSs) are large, modular enzymes that produce bioactive peptides of tremendous structural and chemical diversity, due to the incorporation, alongside the canonical 20 amino acids, of non-proteinogenic amino acids, fatty acids, sugars and heterocyclic rings. For linear NRPSs, the size and composition of the peptide product is dictated by the number, order and specificity of the individual modules, each made of several domains. Given the size and complexity of NRPSs, most in vitro studies have focused on individual domains, di-domains or single modules extracted from the full-length proteins. However, intermodular interactions could play a critical role and regulate the activity of the domains and modules in unpredictable ways. Here we investigate in vitro substrate activation by three A domains of the tyrocidine synthetase TycC enzyme, systematically comparing their activity when alone (with the respective PCP domain), in pairs (di-modular constructs) or all together (tri-modular construct). Furthermore, we study the impact of mutations in the A or PCP domains in these various constructs. Our results suggest that substrate adenylation and effects of mutations largely depend on the context in which the domains/modules are. Therefore, generalizing properties observed for domains or modules in isolation should be done with caution. More... »

PAGES

5119

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-019-41492-8

DOI

http://dx.doi.org/10.1038/s41598-019-41492-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112988006

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30914767


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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This table displays all metadata directly associated to this object as RDF triples.

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