Localization and mutagenesis of the sorting signal binding site on sortase A from Staphylococcus aureus

FEBS Lett. 2004 Jul 30;571(1-3):221-6. doi: 10.1016/j.febslet.2004.06.070.


Surface proteins in Gram-positive bacteria are anchored to the cell wall by the action of sortase enzymes. The Staphylococcus aureus sortase A (SrtA) protein anchors proteins by recognizing a cell wall sorting signal containing the amino acid sequence LPXTG. To understand how SrtA binds this sequence, we carried out NMR studies of new peptidyl-cyanoalkene and peptidyl-sulfhydryl inhibitors that contain the sorting signal sequence LPAT. These studies combined with amino acid mutagenesis identified a catalytically important and conserved binding surface formed by residues A118, T180, and I182. Compatible with its recently proposed role as a general base, R197 is also shown to be required for catalysis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Aminoacyltransferases / chemistry*
  • Aminoacyltransferases / genetics
  • Aminoacyltransferases / metabolism*
  • Bacterial Proteins
  • Binding Sites
  • Cell Wall / enzymology
  • Cysteine Endopeptidases
  • Enzyme Inhibitors / pharmacology
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Protein Conformation
  • Signal Transduction
  • Staphylococcus aureus / enzymology*
  • Staphylococcus aureus / genetics


  • Bacterial Proteins
  • Enzyme Inhibitors
  • Aminoacyltransferases
  • sortase A
  • Cysteine Endopeptidases