| Literature DB >> 29309054 |
Matthew Jenner1,2, Simone Kosol1, Daniel Griffiths1, Panward Prasongpholchai1, Lucio Manzi3, Andrew S Barrow3, John E Moses3, Neil J Oldham3, Józef R Lewandowski1, Gregory L Challis1,2.
Abstract
Modular polyketide synthases (PKSs) produce numerous structurally complex natural products that have diverse applications in medicine and agriculture. PKSs typically consist of several multienzyme subunits that utilize structurally defined docking domains (DDs) at their N and C termini to ensure correct assembly into functional multiprotein complexes. Here we report a fundamentally different mechanism for subunit assembly in trans-acyltransferase (trans-AT) modular PKSs at the junction between ketosynthase (KS) and dehydratase (DH) domains. This mechanism involves direct interaction of a largely unstructured docking domain (DD) at the C terminus of the KS with the surface of the downstream DH. Acyl transfer assays and mechanism-based crosslinking established that the DD is required for the KS to communicate with the acyl carrier protein appended to the DH. Two distinct regions for binding of the DD to the DH were identified using NMR spectroscopy, carbene footprinting, and mutagenesis, providing a foundation for future elucidation of the molecular basis for interaction specificity.Entities:
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Year: 2018 PMID： 29309054 PMCID： PMC5846730 DOI： 10.1038/nchembio.2549
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040