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|Title:||Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis||Authors:||Hotta, K.
|Issue Date:||2014||Citation:||Hotta, K., Keegan, R.M., Ranganathan, S., Fang, M., Bibby, J., Winn, M.D., Sato, M., Lian, M., Watanabe, K., Rigden, D.J., Kim, C.-Y. (2014). Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis. Angewandte Chemie - International Edition 53 (3) : 824-828. ScholarBank@NUS Repository. https://doi.org/10.1002/anie.201307404||Abstract:||Echinomycin is a nonribosomal depsipeptide natural product with a range of interesting bioactivities that make it an important target for drug discovery and development. It contains a thioacetal bridge, a unique chemical motif derived from the disulfide bond of its precursor antibiotic triostin A by the action of an S-adenosyl-L-methionine-dependent methyltransferase, Ecm18. The crystal structure of Ecm18 in complex with its reaction products S-adenosyl-L-homocysteine and echinomycin was determined at 1.50 Å resolution. Phasing was achieved using a new molecular replacement package called AMPLE, which automatically derives search models from structure predictions based on ab initio protein modelling. Structural analysis indicates that a combination of proximity effects, medium effects, and catalysis by strain drives the unique transformation of the disulfide bond into the thioacetal linkage. Disulfide to thioacetal: The S-adenosyl-L-methionine (SAM)-dependent methyltransferase Ecm 18 converts the disulfide bond of triostin A into a thioacetal linkage to form echinomycin. The 1.50 Å crystal structure of Ecm 18 in complex with its reaction products S-adenosyl-L-homocysteine (SAH) and echinomycin provides insight into how Ecm 18 catalyzes this unusual transformation. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.||Source Title:||Angewandte Chemie - International Edition||URI:||http://scholarbank.nus.edu.sg/handle/10635/100338||ISSN:||14337851||DOI:||10.1002/anie.201307404|
|Appears in Collections:||Staff Publications|
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