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| | ==Crystal structure of Mtb toxin== | | ==Crystal structure of Mtb toxin== |
| - | <StructureSection load='5cca' size='340' side='right' caption='[[5cca]], [[Resolution|resolution]] 3.20Å' scene=''> | + | <StructureSection load='5cca' size='340' side='right'caption='[[5cca]], [[Resolution|resolution]] 3.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cca]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CCA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CCA FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cca]] is a 2 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=5CCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CCA FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mazF3, MT1134 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</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]] 3.2Å</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=5cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cca OCA], [http://pdbe.org/5cca PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cca RCSB], [http://www.ebi.ac.uk/pdbsum/5cca PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cca ProSAT]</span></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=5cca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cca OCA], [https://pdbe.org/5cca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cca RCSB], [https://www.ebi.ac.uk/pdbsum/5cca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cca ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MAZF3_MYCTO MAZF3_MYCTO]] Toxic component of a type II toxin-antitoxin (TA) module. Acts as an endoribonuclease, cleaving in U-rich regions. Neutralized by cognate antitoxin MazE3.[UniProtKB:P9WIH9] | + | [https://www.uniprot.org/uniprot/MAZF3_MYCTU MAZF3_MYCTU] Toxic component of a type II toxin-antitoxin (TA) module. Acts as an mRNA and 23S rRNA interferase, cleaving predominantly after the first 2 Us in the sequence 5'-UUCCU-3'; in 23S rRNA only cleaves once in the ribosomal A site in dissociated but not intact ribosomes. Cleavage of 23S rRNA inhibits protein translation; the 23S rRNA region cleaved is involved in tRNA-binding in the A site, 30S and 50S subunit interaction and ribosome recycling factor association (PubMed:23650345). Upon expression in E.coli and M.smegmatis inhibits cell growth and colony formation. It dramatically increases persister cell formation in M.smegmatis upon challenge with gentamicin or kanamycin. Overexpression leads to bacteriostasis rather than bacteriocide. Its toxic effect is neutralized by coexpression with cognate antitoxin MazE3.<ref>PMID:16611633</ref> <ref>PMID:19016878</ref> <ref>PMID:20011113</ref> <ref>PMID:20705052</ref> <ref>PMID:23650345</ref> <ref>PMID:25608501</ref> |
| | + | |
| | + | ==See Also== |
| | + | *[[Endonuclease 3D structures|Endonuclease 3D structures]] |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arbing, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Cascio, D]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Eisenberg, D]] | + | [[Category: Arbing M]] |
| - | [[Category: Miallau, L]] | + | [[Category: Cascio D]] |
| - | [[Category: Serrano, V de]] | + | [[Category: Eisenberg D]] |
| - | [[Category: Structural genomic]] | + | [[Category: Miallau L]] |
| - | [[Category: Hydrolase]] | + | [[Category: De Serrano V]] |
| - | [[Category: Persistence]]
| + | |
| - | [[Category: Ribonuclease]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| - | [[Category: Toxin-antitoxin]]
| + | |
| Structural highlights
Function
MAZF3_MYCTU Toxic component of a type II toxin-antitoxin (TA) module. Acts as an mRNA and 23S rRNA interferase, cleaving predominantly after the first 2 Us in the sequence 5'-UUCCU-3'; in 23S rRNA only cleaves once in the ribosomal A site in dissociated but not intact ribosomes. Cleavage of 23S rRNA inhibits protein translation; the 23S rRNA region cleaved is involved in tRNA-binding in the A site, 30S and 50S subunit interaction and ribosome recycling factor association (PubMed:23650345). Upon expression in E.coli and M.smegmatis inhibits cell growth and colony formation. It dramatically increases persister cell formation in M.smegmatis upon challenge with gentamicin or kanamycin. Overexpression leads to bacteriostasis rather than bacteriocide. Its toxic effect is neutralized by coexpression with cognate antitoxin MazE3.[1] [2] [3] [4] [5] [6]
See Also
References
- ↑ Zhu L, Zhang Y, Teh JS, Zhang J, Connell N, Rubin H, Inouye M. Characterization of mRNA interferases from Mycobacterium tuberculosis. J Biol Chem. 2006 Jul 7;281(27):18638-43. Epub 2006 Apr 12. PMID:16611633 doi:http://dx.doi.org/10.1074/jbc.M512693200
- ↑ Gupta A. Killing activity and rescue function of genome-wide toxin-antitoxin loci of Mycobacterium tuberculosis. FEMS Microbiol Lett. 2009 Jan;290(1):45-53. doi:, 10.1111/j.1574-6968.2008.01400.x. Epub 2008 Nov 10. PMID:19016878 doi:http://dx.doi.org/10.1111/j.1574-6968.2008.01400.x
- ↑ Ramage HR, Connolly LE, Cox JS. Comprehensive functional analysis of Mycobacterium tuberculosis toxin-antitoxin systems: implications for pathogenesis, stress responses, and evolution. PLoS Genet. 2009 Dec;5(12):e1000767. doi: 10.1371/journal.pgen.1000767. Epub 2009, Dec 11. PMID:20011113 doi:http://dx.doi.org/10.1371/journal.pgen.1000767
- ↑ Han JS, Lee JJ, Anandan T, Zeng M, Sripathi S, Jahng WJ, Lee SH, Suh JW, Kang CM. Characterization of a chromosomal toxin-antitoxin, Rv1102c-Rv1103c system in Mycobacterium tuberculosis. Biochem Biophys Res Commun. 2010 Sep 24;400(3):293-8. doi:, 10.1016/j.bbrc.2010.08.023. Epub 2010 Aug 10. PMID:20705052 doi:http://dx.doi.org/10.1016/j.bbrc.2010.08.023
- ↑ Schifano JM, Edifor R, Sharp JD, Ouyang M, Konkimalla A, Husson RN, Woychik NA. Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site. Proc Natl Acad Sci U S A. 2013 May 21;110(21):8501-6. doi:, 10.1073/pnas.1222031110. Epub 2013 May 6. PMID:23650345 doi:http://dx.doi.org/10.1073/pnas.1222031110
- ↑ Tiwari P, Arora G, Singh M, Kidwai S, Narayan OP, Singh R. MazF ribonucleases promote Mycobacterium tuberculosis drug tolerance and virulence in guinea pigs. Nat Commun. 2015 Jan 22;6:6059. doi: 10.1038/ncomms7059. PMID:25608501 doi:http://dx.doi.org/10.1038/ncomms7059
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