4NEC

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

Summary for 4NEC

• Entry DOI: 10.2210/pdb4nec/pdb
• Related PRD ID: PRD_000491
• Descriptor: Putative SAM-dependent methyltransferase, Echinomycin, S-ADENOSYL-L-HOMOCYSTEINE, ... (9 entities in total)
• Functional Keywords: methyltransferase, sam-dependent methyltransferase, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Streptomyces lasaliensis; More
• Total number of polymer chains: 8
• Total formula weight: 123693.67

Authors

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. (deposition date: 2013-10-29, release date: 2014-01-15, Last modification date: 2024-04-03)

Primary 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.
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

Experimental method

X-RAY DIFFRACTION (1.5 Å)