1t2p
From Proteopedia
(New page: 200px<br /><applet load="1t2p" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t2p, resolution 2.00Å" /> '''Crystal structure of...) |
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| - | [[Image:1t2p.gif|left|200px]]<br /><applet load="1t2p" size=" | + | [[Image:1t2p.gif|left|200px]]<br /><applet load="1t2p" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1t2p, resolution 2.00Å" /> | caption="1t2p, resolution 2.00Å" /> | ||
'''Crystal structure of Sortase A from Staphylococcus aureus'''<br /> | '''Crystal structure of Sortase A from Staphylococcus aureus'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The cell wall envelope of staphylococci and other Gram-positive pathogens | + | 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 Structure== | ==About this Structure== | ||
| - | 1T2P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http:// | + | 1T2P is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T2P OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Staphylococcus aureus]] | [[Category: Staphylococcus aureus]] | ||
| - | [[Category: Bice, T | + | [[Category: Bice, T W.]] |
| - | [[Category: Narayana, S | + | [[Category: Narayana, S V.]] |
[[Category: Schneewind, O.]] | [[Category: Schneewind, O.]] | ||
[[Category: Ton-That, H.]] | [[Category: Ton-That, H.]] | ||
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[[Category: transpeptidase]] | [[Category: transpeptidase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:15 2008'' |
Revision as of 13:09, 21 February 2008
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Crystal structure of Sortase A from Staphylococcus aureus
Overview
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 Structure
1T2P is a Single protein structure of sequence from Staphylococcus aureus. Full crystallographic information is available from OCA.
Reference
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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