Please use this identifier to cite or link to this item:
|Title:||Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis|
|Authors:||Hotta, K. |
|Source:||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|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 15, 2018
WEB OF SCIENCETM
checked on Feb 5, 2018
checked on Feb 19, 2018
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.