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Title: Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis

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.

Authors:
 [1];  [2];  [1];  [1];  [3];  [4];  [5];  [1];  [5];  [3];  [1]
  1. National Univ. of Singapore (Singapore)
  2. STFC Rutherford Appleton Lab., Oxfordshire (United Kingdom)
  3. Univ. of Liverpool (United Kingdom).
  4. Daresbury Lab., Daresbury (United Kingdom)
  5. Univ. of Shizuoka, Shizouka (Japan)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1191737
Resource Type:
Journal Article
Journal Name:
Angewandte Chemie (International Edition)
Additional Journal Information:
Journal Volume: 53; Journal Issue: 3; Journal ID: ISSN 1433-7851
Country of Publication:
United States
Language:
ENGLISH

Citation Formats

Hotta, Kinya, Keegan, Ronan M., Ranganathan, Soumya, Fang, Minyi, Bibby, Jaclyn, Winn, Martyn D., Sato, Michio, Lian, Mingzhu, Watanabe, Kenji, Rigden, Daniel J., and Kim, Chu-Young. Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis. United States: N. p., 2013. Web. doi:10.1002/anie.201307404.
Hotta, Kinya, Keegan, Ronan M., Ranganathan, Soumya, Fang, Minyi, Bibby, Jaclyn, Winn, Martyn D., Sato, Michio, Lian, Mingzhu, Watanabe, Kenji, Rigden, Daniel J., & Kim, Chu-Young. Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis. United States. https://doi.org/10.1002/anie.201307404
Hotta, Kinya, Keegan, Ronan M., Ranganathan, Soumya, Fang, Minyi, Bibby, Jaclyn, Winn, Martyn D., Sato, Michio, Lian, Mingzhu, Watanabe, Kenji, Rigden, Daniel J., and Kim, Chu-Young. 2013. "Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis". United States. https://doi.org/10.1002/anie.201307404.
@article{osti_1191737,
title = {Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis},
author = {Hotta, Kinya and Keegan, Ronan M. and Ranganathan, Soumya and Fang, Minyi and Bibby, Jaclyn and Winn, Martyn D. and Sato, Michio and Lian, Mingzhu and Watanabe, Kenji and Rigden, Daniel J. and Kim, Chu-Young},
abstractNote = {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.},
doi = {10.1002/anie.201307404},
url = {https://www.osti.gov/biblio/1191737}, journal = {Angewandte Chemie (International Edition)},
issn = {1433-7851},
number = 3,
volume = 53,
place = {United States},
year = {Mon Dec 02 00:00:00 EST 2013},
month = {Mon Dec 02 00:00:00 EST 2013}
}