4NEC

Conversion of a Disulfide Bond into a Thioacetal Group during Echinomycin Biosynthesis

4NEC の概要

• エントリーDOI: 10.2210/pdb4nec/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000491
• 分子名称: Putative SAM-dependent methyltransferase, Echinomycin, S-ADENOSYL-L-HOMOCYSTEINE, ... (9 entities in total)
• 機能のキーワード: methyltransferase, sam-dependent methyltransferase, transferase-antibiotic complex, transferase/antibiotic
• 由来する生物種: Streptomyces lasaliensis; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 123693.67

構造登録者

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. (登録日: 2013-10-29, 公開日: 2014-01-15, 最終更新日: 2024-04-03)

主引用文献

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.
Conversion of a disulfide bond into a thioacetal group during echinomycin biosynthesis.
Angew.Chem.Int.Ed.Engl., 53:824-828, 2014

PubMed 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.

PubMed: 24302672
DOI: 10.1002/anie.201307404

実験手法

X-RAY DIFFRACTION (1.5 Å)