1t2p
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Crystal structure of Sortase A from Staphylococcus aureus
OverviewOverview
The cell wall envelope of staphylococci and other Gram-positive pathogens, is coated with surface proteins that interact with human host tissues., Surface proteins of Staphylococcus aureus are covalently linked to the, cell wall envelope by a mechanism requiring C-terminal sorting signals, with an LPXTG motif. Sortase (SrtA) cleaves surface proteins between the, threonine (T) and the glycine (G) of the LPXTG motif and catalyzes the, formation of an amide bond between threonine at the C-terminal end of, polypeptides and cell wall cross-bridges. The active site architecture and, catalytic mechanism of sortase A has hitherto not been revealed. Here we, present the crystal structures of native SrtA, of an active site mutant of, SrtA, and of the mutant SrtA complexed with its substrate LPETG peptide, and describe the substrate binding pocket of the enzyme. Highly conserved, proline (P) and threonine (T) residues of the LPXTG motif are held in, position by hydrophobic contacts, whereas the glutamic acid residue (E) at, the X position points out into the solvent. The scissile T-G peptide bond, is positioned between the active site Cys(184) and Arg(197) residues and, at a greater distance from the imidazolium side chain of His(120). All, three residues, His(120), Cys(184), and Arg(197), are conserved in sortase, enzymes from Gram-positive bacteria. Comparison of the active sites of S., aureus sortase A and sortase B provides insight into substrate specificity, and suggests a universal sortase-catalyzed mechanism of bacterial surface, protein anchoring in Gram-positive bacteria.
About this StructureAbout this Structure
1T2P is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of Staphylococcus aureus sortase A and its substrate complex., Zong Y, Bice TW, Ton-That H, Schneewind O, Narayana SV, J Biol Chem. 2004 Jul 23;279(30):31383-9. Epub 2004 Apr 26. PMID:15117963
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