6ifc | pdb_00006ifc
Crystal structure of VapBC from Salmonella typhimurium
Structural highlights
Function[VAPC_SALTY] Toxic component of a type II toxin-antitoxin (TA) system. A site-specific tRNA-(fMet) endonuclease, it cleaves both charged and uncharged tRNA-(fMet) between positions 38 and 39 at the anticodon stem-loop boundary. Does not cleave tRNA(Met), tRNA(Arg2), tRNA(His), tRNA(Leu), tRNA(Phe) tRNA(Thr1), tRNA(Tyr) or tRNA(Val). Overexpression in E.coli inhibits translation, leads to loss of cell growth and degradation of tRNA(fMet), these effects are neutralized by expression of cognate antitoxin VapB. Expression also activates translation initiation at correctly positioned elongator codons (AAA and to a lesser extent AAG). Ectopic overexpression in E.coli induces the YoeB toxin, but this is not the cause of VapC toxicity. [VAPB_SALTY] Antitoxin component of a type II toxin-antitoxin (TA) system. Upon expression in E.coli neutralizes the effect of cognate toxin VapC.[1] [2] Publication Abstract from PubMedBacterial toxin-antitoxin (TA) system has gained attention for its essential roles in cellular maintenance and survival under harsh environmental conditions such as nutrient deficiency and antibiotic treatment. There are at least 14 TA systems in Salmonella enterica serovar Typhimurium LT2, a pathogenic bacterium, and none of the structures of these TA systems have been determined. We determined the crystal structure of the VapBC TA complex from S. Typhimurium LT2 in proteolyzed and DNA-bound forms at 2.0 A and 2.8 A resolution, respectively. The VapC toxin possesses a pilT N-terminal domain (PIN-domain) that shows ribonuclease activity, and the VapB antitoxin has an AbrB-type DNA binding domain. In addition, the structure revealed details of interaction mode between VapBC and the cognate promoter DNA, including the inhibition of VapC by VapB and linear conformation of bound DNA in the VapBC complex. The complexation of VapBC with the linear DNA is not consistent with known structures of VapBC homologs in complex with bent DNA. We also identified VapC from S. Typhimurium LT2 as a putative Ca(2+) -dependent ribonuclease, which differs from previous data showing that VapC homologs have Mg(2+) or Mn(2+) -dependent ribonuclease activities. The present studies could provide structural understanding of the physiology of VapBC systems and foundation for the development of new antibiotic drugs against Salmonella infection. Crystal structure of proteolyzed VapBC and DNA-bound VapBC from Salmonella enterica Typhimurium LT2 and VapC as a putative Ca(2+) -dependent ribonuclease.,Park D, Yoon HJ, Lee KY, Park SJ, Cheon SH, Lee HH, Lee SJ, Lee BJ FASEB J. 2019 Dec 23. doi: 10.1096/fj.201901989R. PMID:31908032[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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