5cca

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Crystal structure of Mtb toxin

Structural highlights

5cca is a 2 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ 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
  6. ↑ 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

Contents


PDB ID 5cca

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