Structure of the bacterial teichoic acid polymerase TagF provides insights into membrane association and catalysis.
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.
Lovering
Andrew L
AL
Department of Biochemistry and Molecular Biology, Vancouver, Canada.
Lin
Leo Y-C
LY
Sewell
Edward W
EW
Spreter
Thomas
T
Brown
Eric D
ED
Strynadka
Natalie C J
NC
D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009702:Nucleoside Diphosphate Sugars / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D013212:Staphylococcus epidermidis / Q000201:enzymology*; D013682:Teichoic Acids / Q000737:chemistry / Q000378:metabolism*; D017855:Transferases (Other Substituted Phosphate Groups) / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D009702:Nucleoside Diphosphate Sugars; D013682:Teichoic Acids; C100068:cytidine diphosphate glycerol; D017855:Transferases (Other Substituted Phosphate Groups); C072175:CDP glycerol glycerophosphotransferase
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