PLoS Pathogens (Apr 2019)

Structure and mechanism of TagA, a novel membrane-associated glycosyltransferase that produces wall teichoic acids in pathogenic bacteria.

  • Michele D Kattke,
  • Jason E Gosschalk,
  • Orlando E Martinez,
  • Garima Kumar,
  • Robert T Gale,
  • Duilio Cascio,
  • Michael R Sawaya,
  • Martin Philips,
  • Eric D Brown,
  • Robert T Clubb

DOI
https://doi.org/10.1371/journal.ppat.1007723
Journal volume & issue
Vol. 15, no. 4
p. e1007723

Abstract

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Staphylococcus aureus and other bacterial pathogens affix wall teichoic acids (WTAs) to their surface. These highly abundant anionic glycopolymers have critical functions in bacterial physiology and their susceptibility to β-lactam antibiotics. The membrane-associated TagA glycosyltransferase (GT) catalyzes the first-committed step in WTA biosynthesis and is a founding member of the WecB/TagA/CpsF GT family, more than 6,000 enzymes that synthesize a range of extracellular polysaccharides through a poorly understood mechanism. Crystal structures of TagA from T. italicus in its apo- and UDP-bound states reveal a novel GT fold, and coupled with biochemical and cellular data define the mechanism of catalysis. We propose that enzyme activity is regulated by interactions with the bilayer, which trigger a structural change that facilitates proper active site formation and recognition of the enzyme's lipid-linked substrate. These findings inform upon the molecular basis of WecB/TagA/CpsF activity and could guide the development of new anti-microbial drugs.