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| | ==Crystal structure of M. tuberculosis MazF-mt3 T52D-F62D mutant in complex with 8-mer RNA== | | ==Crystal structure of M. tuberculosis MazF-mt3 T52D-F62D mutant in complex with 8-mer RNA== |
| - | <StructureSection load='5hkc' size='340' side='right' caption='[[5hkc]], [[Resolution|resolution]] 1.68Å' scene=''> | + | <StructureSection load='5hkc' size='340' side='right'caption='[[5hkc]], [[Resolution|resolution]] 1.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hkc]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HKC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HKC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hkc]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] and [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HKC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HKC FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DU:2-DEOXYURIDINE-5-MONOPHOSPHATE'>DU</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]] 1.68Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hk3|5hk3]], [[5hjz|5hjz]], [[5hk0|5hk0]]</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=5hkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hkc OCA], [https://pdbe.org/5hkc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hkc RCSB], [https://www.ebi.ac.uk/pdbsum/5hkc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hkc 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=5hkc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hkc OCA], [http://pdbe.org/5hkc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hkc RCSB], [http://www.ebi.ac.uk/pdbsum/5hkc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hkc ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MAZF6_MYCTO MAZF6_MYCTO]] Toxic component of a type II toxin-antitoxin (TA) module. Acts as an endoribonuclease on single-strand RNA, cleaving between the second and third bases in the sequences CUCCU and UUCCU. Neutralized by coexpression with cognate antitoxin MazE6.[UniProtKB:P9WII3] | + | [https://www.uniprot.org/uniprot/MAZF6_MYCTU MAZF6_MYCTU] Toxic component of a type II toxin-antitoxin (TA) module. Upon expression in E.coli and in M.smegmatis partially inhibits cell growth and colony formation; its toxic effect is neutralized by coexpression with cognate antitoxin MazE6. Acts as an mRNA interferase on ssRNA, cleaving between the second and third bases in the sequences CUCCU and UUCCU (PubMed:18485066). Further experiments demonstrate that it digests between the first and second bases of UCCUU, yielding a 5'-hydroxyl end; digests M.tuberculosis mRNA (in coding as well as the 5'- and 3'-UTR regions) and 23S rRNA, digests E.coli 16S rRNA both alone and in the 70S ribosome but no data for M.tuberculosis 16S rRNA cleavage was presented. 23S and 16S rRNA digestion occurs in predicted single-stranded regions, the 16S rRNA UCCUU site is in the anti-Shine-Dalgarno site and would cleave off the last 7 nucleotides (PubMed:24709835). Non-cognate antitoxins VapB27 and VapB40 partially neutralize toxicity in vivo (PubMed:20876537).<ref>PMID:17623030</ref> <ref>PMID:18258191</ref> <ref>PMID:18485066</ref> <ref>PMID:19016878</ref> <ref>PMID:20011113</ref> <ref>PMID:20876537</ref> <ref>PMID:24709835</ref> <ref>PMID:25608501</ref> |
| | + | == References == |
| | + | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brennan, R G]] | + | [[Category: Large Structures]] |
| - | [[Category: Yen, T J]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Hydrolase-rna complex]] | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: Mazf]] | + | [[Category: Brennan RG]] |
| - | [[Category: Toxin-antitoxin system]] | + | [[Category: Yen TJ]] |
| Structural highlights
Function
MAZF6_MYCTU Toxic component of a type II toxin-antitoxin (TA) module. Upon expression in E.coli and in M.smegmatis partially inhibits cell growth and colony formation; its toxic effect is neutralized by coexpression with cognate antitoxin MazE6. Acts as an mRNA interferase on ssRNA, cleaving between the second and third bases in the sequences CUCCU and UUCCU (PubMed:18485066). Further experiments demonstrate that it digests between the first and second bases of UCCUU, yielding a 5'-hydroxyl end; digests M.tuberculosis mRNA (in coding as well as the 5'- and 3'-UTR regions) and 23S rRNA, digests E.coli 16S rRNA both alone and in the 70S ribosome but no data for M.tuberculosis 16S rRNA cleavage was presented. 23S and 16S rRNA digestion occurs in predicted single-stranded regions, the 16S rRNA UCCUU site is in the anti-Shine-Dalgarno site and would cleave off the last 7 nucleotides (PubMed:24709835). Non-cognate antitoxins VapB27 and VapB40 partially neutralize toxicity in vivo (PubMed:20876537).[1] [2] [3] [4] [5] [6] [7] [8]
References
- ↑ Carroll P, Brown AC, Hartridge AR, Parish T. Expression of Mycobacterium tuberculosis Rv1991c using an arabinose-inducible promoter demonstrates its role as a toxin. FEMS Microbiol Lett. 2007 Sep;274(1):73-82. Epub 2007 Jul 9. PMID:17623030 doi:http://dx.doi.org/10.1111/j.1574-6968.2007.00842.x
- ↑ Zhao L, Zhang J. Biochemical characterization of a chromosomal toxin-antitoxin system in Mycobacterium tuberculosis. FEBS Lett. 2008 Mar 5;582(5):710-4. doi: 10.1016/j.febslet.2008.01.045. Epub 2008, Feb 5. PMID:18258191 doi:http://dx.doi.org/10.1016/j.febslet.2008.01.045
- ↑ Zhu L, Phadtare S, Nariya H, Ouyang M, Husson RN, Inouye M. The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA. Mol Microbiol. 2008 Aug;69(3):559-69. doi: 10.1111/j.1365-2958.2008.06284.x. Epub, 2008 Jun 28. PMID:18485066 doi:http://dx.doi.org/10.1111/j.1365-2958.2008.06284.x
- ↑ 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
- ↑ Zhu L, Sharp JD, Kobayashi H, Woychik NA, Inouye M. Noncognate Mycobacterium tuberculosis toxin-antitoxins can physically and functionally interact. J Biol Chem. 2010 Dec 17;285(51):39732-8. doi: 10.1074/jbc.M110.163105. Epub 2010, Sep 27. PMID:20876537 doi:http://dx.doi.org/10.1074/jbc.M110.163105
- ↑ Schifano JM, Vvedenskaya IO, Knoblauch JG, Ouyang M, Nickels BE, Woychik NA. An RNA-seq method for defining endoribonuclease cleavage specificity identifies dual rRNA substrates for toxin MazF-mt3. Nat Commun. 2014 Apr 8;5:3538. doi: 10.1038/ncomms4538. PMID:24709835 doi:http://dx.doi.org/10.1038/ncomms4538
- ↑ 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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