4NEC: Conversion of a Disulfide Bond Into a Thioacetal Group During Echinomycin Biosynthesis

Citation:
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 A 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.
PDB ID: 4NECDownload
MMDB ID: 116693
PDB Deposition Date: 2013/10/29
Updated in MMDB: 2014/01 
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4NEC: dimeric; determined by author and by software (PISA)
Molecular Components in 4NEC
Label Count Molecule
Protein (1 molecule)
1
Putative Sam-dependent Methyltransferase
Molecule annotation
Nucleotide(1 molecule)
1
Echinomycin
Molecule annotation
Chemicals (6 molecules)
1
1
2
1
3
1
4
2
5
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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