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| | ==Crystal Structure of Enhanced Intracellular Survival (Eis) Protein from Mycobacterium tuberculosis with Acetyl CoA== | | ==Crystal Structure of Enhanced Intracellular Survival (Eis) Protein from Mycobacterium tuberculosis with Acetyl CoA== |
| - | <StructureSection load='3ryo' size='340' side='right' caption='[[3ryo]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3ryo' size='340' side='right'caption='[[3ryo]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ryo]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RYO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RYO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ryo]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RYO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RYO FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACO:ACETYL+COENZYME+*A'>ACO</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]] 2.8Å</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=ACO:ACETYL+COENZYME+*A'>ACO</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3sxn|3sxn]], [[3uy5|3uy5]]</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=3ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ryo OCA], [https://pdbe.org/3ryo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ryo RCSB], [https://www.ebi.ac.uk/pdbsum/3ryo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ryo ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">eis, Rv2416c, MT2489, MTCY253.04 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])</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=3ryo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ryo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ryo RCSB], [http://www.ebi.ac.uk/pdbsum/3ryo PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/EIS_MYCTU EIS_MYCTU]] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.<ref>PMID:10629183</ref> | + | [https://www.uniprot.org/uniprot/EIS_MYCTU EIS_MYCTU] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.<ref>PMID:10629183</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3ryo" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycobacterium tuberculosis]] | | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: An, D R]] | + | [[Category: An DR]] |
| - | [[Category: Im, H N]] | + | [[Category: Im HN]] |
| - | [[Category: Kim, D J]] | + | [[Category: Kim DJ]] |
| - | [[Category: Kim, H J]] | + | [[Category: Kim HJ]] |
| - | [[Category: Kim, H S]] | + | [[Category: Kim HS]] |
| - | [[Category: Kim, J]] | + | [[Category: Kim J]] |
| - | [[Category: Kim, K H]] | + | [[Category: Kim KH]] |
| - | [[Category: Lee, J Y]] | + | [[Category: Lee JY]] |
| - | [[Category: Lee, S J]] | + | [[Category: Lee SJ]] |
| - | [[Category: Song, J]] | + | [[Category: Song J]] |
| - | [[Category: Suh, S W]] | + | [[Category: Suh SW]] |
| - | [[Category: Yoon, H J]] | + | [[Category: Yoon HJ]] |
| - | [[Category: Yoon, J Y]] | + | [[Category: Yoon JY]] |
| - | [[Category: Acetyltransferase]]
| + | |
| - | [[Category: Gnat]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
EIS_MYCTU May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.[1]
Publication Abstract from PubMed
The intracellular pathogen Mycobacterium tuberculosis (Mtb) causes tuberculosis. Enhanced intracellular survival (Eis) protein, secreted by Mtb, enhances survival of Mycobacterium smegmatis (Msm) in macrophages. Mtb Eis was shown to suppress host immune defenses by negatively modulating autophagy, inflammation, and cell death through JNK-dependent inhibition of reactive oxygen species (ROS) generation. Mtb Eis was recently demonstrated to contribute to drug resistance by acetylating multiple amines of aminoglycosides. However, the mechanism of enhanced intracellular survival by Mtb Eis remains unanswered. Therefore, we have characterized both Mtb and Msm Eis proteins biochemically and structurally. We have discovered that Mtb Eis is an efficient N(epsilon)-acetyltransferase, rapidly acetylating Lys55 of dual-specificity protein phosphatase 16 (DUSP16)/mitogen-activated protein kinase phosphatase-7 (MKP-7), a JNK-specific phosphatase. In contrast, Msm Eis is more efficient as an N(alpha)-acetyltransferase. We also show that Msm Eis acetylates aminoglycosides as readily as Mtb Eis. Furthermore, Mtb Eis, but not Msm Eis, inhibits LPS-induced JNK phosphorylation. This functional difference against DUSP16/MKP-7 can be understood by comparing the structures of two Eis proteins. The active site of Mtb Eis with a narrow channel seems more suitable for sequence-specific recognition of the protein substrate than the pocket-shaped active site of Msm Eis. We propose that Mtb Eis initiates the inhibition of JNK-dependent autophagy, phagosome maturation, and ROS generation by acetylating DUSP16/MKP-7. Our work thus provides insight into the mechanism of suppressing host immune responses and enhancing mycobacterial survival within macrophages by Mtb Eis.
Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7.,Kim KH, An DR, Song J, Yoon JY, Kim HS, Yoon HJ, Im HN, Kim J, Kim do J, Lee SJ, Kim KH, Lee HM, Kim HJ, Jo EK, Lee JY, Suh SW Proc Natl Acad Sci U S A. 2012 May 15;109(20):7729-34. Epub 2012 Apr 30. PMID:22547814[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wei J, Dahl JL, Moulder JW, Roberts EA, O'Gaora P, Young DB, Friedman RL. Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J Bacteriol. 2000 Jan;182(2):377-84. PMID:10629183
- ↑ Kim KH, An DR, Song J, Yoon JY, Kim HS, Yoon HJ, Im HN, Kim J, Kim do J, Lee SJ, Kim KH, Lee HM, Kim HJ, Jo EK, Lee JY, Suh SW. Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc Natl Acad Sci U S A. 2012 May 15;109(20):7729-34. Epub 2012 Apr 30. PMID:22547814 doi:10.1073/pnas.1120251109
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