2oqz: Difference between revisions

Line 4:

==Overview==

Sortases anchor surface proteins to the cell wall of Gram-positive, pathogens through recognition of specific motif sequences. Loss of sortase, leads to large reductions in virulence, which identifies sortase as a, target for the development of antibacterials. By screening 135,625 small, molecules for inhibition, we report here that aryl (beta-amino)ethyl, ketones inhibit sortase enzymes from staphylococci and bacilli. Inhibition, of sortases occurs through an irreversible, covalent modification of their, active site cysteine. Sortases specifically activate this class of, molecules via beta-elimination, generating a reactive olefin intermediate, that covalently modifies the cysteine thiol. Analysis of the, three-dimensional structure of Bacillus anthracis sortase B with and, without inhibitor provides insights into the mechanism of inhibition and, reveals binding pockets that can be exploited for drug discovery.

Sortases anchor surface proteins to the cell wall of Gram-positive pathogens through recognition of specific motif sequences. Loss of sortase leads to large reductions in virulence, which identifies sortase as a target for the development of antibacterials. By screening 135,625 small molecules for inhibition, we report here that aryl (beta-amino)ethyl ketones inhibit sortase enzymes from staphylococci and bacilli. Inhibition of sortases occurs through an irreversible, covalent modification of their active site cysteine. Sortases specifically activate this class of molecules via beta-elimination, generating a reactive olefin intermediate that covalently modifies the cysteine thiol. Analysis of the three-dimensional structure of Bacillus anthracis sortase B with and without inhibitor provides insights into the mechanism of inhibition and reveals binding pockets that can be exploited for drug discovery.

==About this Structure==

Line 14:

[[Category: Cruzipain]]

[[Category: Single protein]]

[[Category: GLRCE, The.Great.Lakes.Regional.Center.of.Excellence.]]

[[Category: GLRCE, The Great Lakes Regional Center of Excellence.]]

[[Category: Joachimiak, A.]]

[[Category: Maresso, A.W.]]

[[Category: Maresso, A W.]]

[[Category: Schneewind, O.]]

[[Category: Wu, R.]]

[[Category: Zhang, R.]]

[[Category: ACY]]

[[Category: b.anthracis]]

[[Category: b anthracis]]

[[Category: inhibitor]]

[[Category: sortase b protein]]

[[Category: the great lakes regional center of excellence (glrce)]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Wed Jan 23 13~~:43:07 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:36 2008''

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 4: / Line 4: @@
 ==Overview==
-Sortases anchor surface proteins to the cell wall of Gram-positive, pathogens through recognition of specific motif sequences. Loss of sortase, leads to large reductions in virulence, which identifies sortase as a, target for the development of antibacterials. By screening 135,625 small, molecules for inhibition, we report here that aryl (beta-amino)ethyl, ketones inhibit sortase enzymes from staphylococci and bacilli. Inhibition, of sortases occurs through an irreversible, covalent modification of their, active site cysteine. Sortases specifically activate this class of, molecules via beta-elimination, generating a reactive olefin intermediate, that covalently modifies the cysteine thiol. Analysis of the, three-dimensional structure of Bacillus anthracis sortase B with and, without inhibitor provides insights into the mechanism of inhibition and, reveals binding pockets that can be exploited for drug discovery.
+Sortases anchor surface proteins to the cell wall of Gram-positive pathogens through recognition of specific motif sequences. Loss of sortase leads to large reductions in virulence, which identifies sortase as a target for the development of antibacterials. By screening 135,625 small molecules for inhibition, we report here that aryl (beta-amino)ethyl ketones inhibit sortase enzymes from staphylococci and bacilli. Inhibition of sortases occurs through an irreversible, covalent modification of their active site cysteine. Sortases specifically activate this class of molecules via beta-elimination, generating a reactive olefin intermediate that covalently modifies the cysteine thiol. Analysis of the three-dimensional structure of Bacillus anthracis sortase B with and without inhibitor provides insights into the mechanism of inhibition and reveals binding pockets that can be exploited for drug discovery.
 ==About this Structure==
@@ Line 14: / Line 14: @@
 [[Category: Cruzipain]]
 [[Category: Single protein]]
-[[Category: GLRCE, The.Great.Lakes.Regional.Center.of.Excellence.]]
+[[Category: GLRCE, The Great Lakes Regional Center of Excellence.]]
 [[Category: Joachimiak, A.]]
-[[Category: Maresso, A.W.]]
+[[Category: Maresso, A W.]]
 [[Category: Schneewind, O.]]
 [[Category: Wu, R.]]
 [[Category: Zhang, R.]]
 [[Category: ACY]]
-[[Category: b.anthracis]]
+[[Category: b anthracis]]
 [[Category: inhibitor]]
 [[Category: sortase b protein]]
 [[Category: the great lakes regional center of excellence (glrce)]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:43:07 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:21:36 2008''