2oqz
From Proteopedia
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| - | [[Image:2oqz.jpg|left|200px]] | ||
| - | + | ==The crystal structure of sortase B from B.anthracis in complex with AAEK2== | |
| - | + | <StructureSection load='2oqz' size='340' side='right'caption='[[2oqz]], [[Resolution|resolution]] 1.60Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | | | + | <table><tr><td colspan='2'>[[2oqz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Ames Bacillus anthracis str. Ames]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OQZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OQZ FirstGlance]. <br> |
| - | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=CS4:S-[3-(3,4-DICHLOROPHENYL)-3-OXOPROPYL]-L-CYSTEINE'>CS4</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | |
| - | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2oqz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oqz OCA], [https://pdbe.org/2oqz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2oqz RCSB], [https://www.ebi.ac.uk/pdbsum/2oqz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2oqz ProSAT]</span></td></tr> | |
| - | + | </table> | |
| - | + | == Function == | |
| - | + | [https://www.uniprot.org/uniprot/A0A6L8PZR0_BACAN A0A6L8PZR0_BACAN] | |
| - | + | == Evolutionary Conservation == | |
| - | == | + | [[Image:Consurf_key_small.gif|200px|right]] |
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/oq/2oqz_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2oqz ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
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. | ||
| - | + | Activation of inhibitors by sortase triggers irreversible modification of the active site.,Maresso AW, Wu R, Kern JW, Zhang R, Janik D, Missiakas DM, Duban ME, Joachimiak A, Schneewind O J Biol Chem. 2007 Aug 10;282(32):23129-39. Epub 2007 Jun 1. PMID:17545669<ref>PMID:17545669</ref> | |
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| - | Activation of inhibitors by sortase triggers irreversible modification of the active site., Maresso AW, Wu R, Kern JW, Zhang R, Janik D, Missiakas DM, Duban ME, Joachimiak A, Schneewind O | + | |
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| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2oqz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bacillus anthracis str. Ames]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Joachimiak A]] | ||
| + | [[Category: Maresso AW]] | ||
| + | [[Category: Schneewind O]] | ||
| + | [[Category: Wu R]] | ||
| + | [[Category: Zhang R]] | ||
Current revision
The crystal structure of sortase B from B.anthracis in complex with AAEK2
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