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7awk

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Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)Crystal structure of the HigB1 toxin mutant K95A from Mycobacterium tuberculosis (Rv1955)

Structural highlights

7awk is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[HIGB1_MYCTU] Toxic component of an atypical, type II toxin-antitoxin chaperone (TAC) system. Upon expression in M.smegmatis inhibits colony formation and cell growth (PubMed:20011113, PubMed:23927792). Ectopic expression in wild-type M.tuberculosis has no effect on cell growth; ectopic expression in a triple higB1-higA1-Rv1957 (delta TAC) disruption mutant causes growth arrest, killing a considerable proportion of the cells. Increased ectopic expression leads to decreased levels of IdeR- and Zur-regulated genes as well as cleavage within the mRNA region of tmRNA (transfer-mRNA), strongly suggesting it is an endoribonuclease; also degrades E.coli and M-smegmatis tmRNA (PubMed:23927792). Its toxic effect is neutralized by coexpression with antitoxin HigA. Neutralization of HigB1 toxin in E.coli or M.marinum also requires SecB-like chaperone Rv1957, making this the first toxin-antitoxin chaperone (TAC) system (PubMed:21536872).[1] [2] [3] [4]

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Bordes P, Cirinesi AM, Ummels R, Sala A, Sakr S, Bitter W, Genevaux P. SecB-like chaperone controls a toxin-antitoxin stress-responsive system in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2011 May 17;108(20):8438-43. doi:, 10.1073/pnas.1101189108. Epub 2011 May 2. PMID:21536872 doi:http://dx.doi.org/10.1073/pnas.1101189108
  4. ↑ Schuessler DL, Cortes T, Fivian-Hughes AS, Lougheed KE, Harvey E, Buxton RS, Davis EO, Young DB. Induced ectopic expression of HigB toxin in Mycobacterium tuberculosis results in growth inhibition, reduced abundance of a subset of mRNAs and cleavage of tmRNA. Mol Microbiol. 2013 Oct;90(1):195-207. doi: 10.1111/mmi.12358. Epub 2013 Aug 23. PMID:23927792 doi:http://dx.doi.org/10.1111/mmi.12358

7awk, resolution 1.91Å

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