4OXI: Crystal Structure Of Vibrio Cholerae Adenylation Domain Alme In Complex With Glycyl-adenosine-5'-phosphate

The current pandemic El Tor biotype of O1 Vibrio cholerae is resistant to polymyxins, whereas the previous pandemic strain of the classical biotype is polymyxin sensitive. The almEFG operon found in El Tor V. cholerae confers >100-fold resistance to polymyxins through the glycylation of lipopolysaccharide. Here, we present the mechanistic determination of initial steps in the AlmEFG pathway. We verify that AlmF is an aminoacyl carrier protein and identify AlmE as the enzyme required to activate AlmF as a functional carrier protein. A combination of structural information and activity assays was used to identify a pair of active site residues that are important for mediating AlmE glycine specificity. Overall, the structure of AlmE in complex with its glycyl-adenylate intermediate reveals that AlmE is related to Gram-positive d-alanine/d-alanyl carrier protein ligase, while the trio of proteins in the AlmEFG system forms a chemical pathway that resembles the division of labor in nonribosomal peptide synthetases.
PDB ID: 4OXIDownload
MMDB ID: 125771
PDB Deposition Date: 2014/2/4
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 2.26  Å
Source Organism:
Similar Structures:
Biological Unit for 4OXI: monomeric; determined by author and by software (PISA)
Molecular Components in 4OXI
Label Count Molecule
Protein (1 molecule)
Enterobactin Synthetase Component F-related Protein
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB