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| | ==Crystal structure of acetyltransferase from Bacillus anthracis== | | ==Crystal structure of acetyltransferase from Bacillus anthracis== |
| - | <StructureSection load='3n7z' size='340' side='right' caption='[[3n7z]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='3n7z' size='340' side='right'caption='[[3n7z]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3n7z]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacillus_anthracis_(strain_sterne) Bacillus anthracis (strain sterne)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N7Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3N7Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3n7z]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_anthracis_str._Sterne Bacillus anthracis str. Sterne]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3N7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3N7Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.75Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BAS2743 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=260799 Bacillus anthracis (strain Sterne)])</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=3n7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n7z OCA], [https://pdbe.org/3n7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3n7z RCSB], [https://www.ebi.ac.uk/pdbsum/3n7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3n7z ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3n7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3n7z OCA], [http://pdbe.org/3n7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3n7z RCSB], [http://www.ebi.ac.uk/pdbsum/3n7z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3n7z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
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| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n7/3n7z_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/n7/3n7z_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chang, C]] | + | [[Category: Bacillus anthracis str. Sterne]] |
| - | [[Category: Gornicki, P]] | + | [[Category: Large Structures]] |
| - | [[Category: Joachimiak, A]] | + | [[Category: Chang C]] |
| - | [[Category: Structural genomic]] | + | [[Category: Gornicki P]] |
| - | [[Category: Wu, R]] | + | [[Category: Joachimiak A]] |
| - | [[Category: Zhang, R]] | + | [[Category: Wu R]] |
| - | [[Category: Mcsg]] | + | [[Category: Zhang R]] |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Proteins from the enhanced intracellular survival (Eis) family are versatile acetyltransferases that acetylate amines at multiple positions of several aminoglycosides (AGs). Their upregulation confers drug resistance. Homologues of Eis are present in diverse bacteria, including many pathogens. Eis from Mycobacterium tuberculosis (Eis_Mtb) has been well characterized. In this study, we explored the AG specificity and catalytic efficiency of the Eis family protein from Bacillus anthracis (Eis_Ban). Kinetic analysis of specificity and catalytic efficiency of acetylation of six AGs indicates that Eis_Ban displays significant differences from Eis_Mtb in both substrate binding and catalytic efficiency. The number of acetylated amines was also different for several AGs, indicating a distinct regiospecificity of Eis_Ban. Furthermore, most recently identified inhibitors of Eis_Mtb did not inhibit Eis_Ban, underscoring the differences between these two enzymes. To explain these differences, we determined an Eis_Ban crystal structure. The comparison of the crystal structures of Eis_Ban and Eis_Mtb demonstrates that critical residues lining their respective substrate binding pockets differ substantially, explaining their distinct specificities. Our results suggest that acetyltransferases of the Eis family evolved divergently to garner distinct specificities while conserving catalytic efficiency, possibly to counter distinct chemical challenges. The unique specificity features of these enzymes can be utilized as tools for developing AGs with novel modifications and help guide specific AG treatments to avoid Eis-mediated resistance.
Biochemical and Structural Analysis of an Eis Family Aminoglycoside Acetyltransferase from Bacillus anthracis.,Green KD, Biswas T, Chang C, Wu R, Chen W, Janes BK, Chalupska D, Gornicki P, Hanna PC, Tsodikov OV, Joachimiak A, Garneau-Tsodikova S Biochemistry. 2015 May 26;54(20):3197-206. doi: 10.1021/acs.biochem.5b00244. Epub, 2015 May 12. PMID:25928210[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Green KD, Biswas T, Chang C, Wu R, Chen W, Janes BK, Chalupska D, Gornicki P, Hanna PC, Tsodikov OV, Joachimiak A, Garneau-Tsodikova S. Biochemical and Structural Analysis of an Eis Family Aminoglycoside Acetyltransferase from Bacillus anthracis. Biochemistry. 2015 May 26;54(20):3197-206. doi: 10.1021/acs.biochem.5b00244. Epub, 2015 May 12. PMID:25928210 doi:http://dx.doi.org/10.1021/acs.biochem.5b00244
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