4K3T: Crystal Structure of Glycopeptide Hexose Oxidase Dbv29 Complexed With Teicoplanin

Citation:
Abstract
In the search for new efficacious antibiotics, biosynthetic engineering offers attractive opportunities to introduce minor alterations to antibiotic structures that may overcome resistance. Dbv29, a flavin-containing oxidase, catalyzes the four-electron oxidation of a vancomycin-like glycopeptide to yield A40926. Structural and biochemical examination of Dbv29 now provides insights into residues that govern flavinylation and activity, protein conformation and reaction mechanism. In particular, the serendipitous discovery of a reaction intermediate in the crystal structure led us to identify an unexpected opportunity to intercept the normal enzyme mechanism at two different points to create new teicoplanin analogs. Using this method, we synthesized families of antibiotic analogs with amidated and aminated lipid chains, some of which showed marked potency and efficacy against multidrug resistant pathogens. This method offers a new strategy for the development of chemical diversity to combat antibacterial resistance.
PDB ID: 4K3TDownload
MMDB ID: 110584
PDB Deposition Date: 2013/4/11
Updated in MMDB: 2013/05
Experimental Method:
x-ray diffraction
Resolution: 1.93  Å
Source Organism:

*This MMDB ID is obsolete.

Molecular Components in 4K3T
Label Count Molecule
Proteins (4 molecules)
4
Putative Hexose Oxidase
Molecule annotation
Chemicals (45 molecules)
1
8
2
4
3
5
4
8
5
8
6
6
7
6
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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