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Insights into protein-protein and enzyme-substrate interactions in modular polyketide synthases
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Tran, Lucky, Broadhurst, R. William, Tosin, Manuela, Cavalli, Andrea and Weissman, Kira J. (2010) Insights into protein-protein and enzyme-substrate interactions in modular polyketide synthases. Chemistry & Biology, Vol.17 (No.7). pp. 705-716. doi:10.1016/j.chembiol.2010.05.017 ISSN 1074-5521.
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Official URL: http://dx.doi.org/10.1016/j.chembiol.2010.05.017
Abstract
Numerous natural products of clinical value are biosynthesized by polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs), which are multienzymes comprising modules of catalytic domains. The key players in each module are carrier proteins, which serve as attachment points for the growing substrate chains. Thus, the details of carrier protein-based substrate delivery to each active site are central to understanding chain assembly in these systems. In the enterobactin NRPS, communication between a peptidyl carrier protein (PCP) and the adjacent thioesterase (TE) domain occurs through formation of a compact complex. Using NMR, we show that the corresponding interaction between a PKS acyl carrier protein (ACP) and its downstream TE is fundamentally different: chain transfer occurs in the absence of a protein-protein interface, with contact limited to the substrate acyl terminus.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QP Physiology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry | ||||
Library of Congress Subject Headings (LCSH): | Protein-protein interactions, Polyketides -- Synthesis, Carrier proteins, Enzymes | ||||
Journal or Publication Title: | Chemistry & Biology | ||||
Publisher: | Cell Press | ||||
ISSN: | 1074-5521 | ||||
Official Date: | 2010 | ||||
Dates: |
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Volume: | Vol.17 | ||||
Number: | No.7 | ||||
Page Range: | pp. 705-716 | ||||
DOI: | 10.1016/j.chembiol.2010.05.017 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Funder: | Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||
Grant number: | 8/B18119 (BBSRC) |
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