Abstract:
Teichoic acid polymers are composed of polyol-phosphate units and form a major component of Gram-positive bacterial cell walls. These anionic compounds perform a multitude of important roles in bacteria and are synthesized by monotopic membrane proteins of the TagF polymerase family. We have determined the structure of Staphylococcus epidermidis TagF to 2.7-A resolution from a construct that includes both the membrane-targeting region and the glycerol-phosphate polymerase domains. TagF possesses a helical region for interaction with the lipid bilayer, placing the active site at a suitable distance for access to the membrane-bound substrate. Characterization of active-site residue variants and analysis of a CDP-glycerol substrate complex suggest a mechanism for polymer synthesis. With the importance of teichoic acid in Gram-positive physiology, this elucidation of the molecular details of TagF function provides a critical new target in the development of novel anti-infectives.
Authors:
Lovering AL, Lin LY, Sewell EW, Spreter T, Brown ED, Strynadka NC.
Reference:
Nat Struct Mol Biol. 2010 May;17(5):582-9. doi: 10.1038/nsmb.1819. Epub 2010 Apr 18.