Crystal structure of the plasmid maintenance system epsilon/zeta: functional mechanism of toxin zeta and inactivation by epsilon 2 zeta 2 complex formation

Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1661-6. doi: 10.1073/pnas.0434325100. Epub 2003 Feb 5.


Programmed cell death in prokaryotes is frequently found as postsegregational killing. It relies on antitoxin/toxin systems that secure stable inheritance of low and medium copy number plasmids during cell division and kill cells that have lost the plasmid. The broad-host-range, low-copy-number plasmid pSM19035 from Streptococcus pyogenes carries the genes encoding the antitoxin/toxin system epsilon/zeta and antibiotic resistance proteins, among others. The crystal structure of the biologically nontoxic epsilon(2)zeta(2) protein complex at a 1.95-A resolution and site-directed mutagenesis showed that free zeta acts as phosphotransferase by using ATPGTP. In epsilon(2)zeta(2), the toxin zeta is inactivated because the N-terminal helix of the antitoxin epsilon blocks the ATPGTP-binding site. To our knowledge, this is the first prokaryotic postsegregational killing system that has been entirely structurally characterized.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antitoxins / pharmacology
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / genetics
  • Bacterial Toxins / pharmacology*
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Mutagenesis
  • Operon
  • Plasmids*
  • Protein Conformation
  • Protein Folding
  • Sequence Homology, Amino Acid
  • Streptococcus pyogenes / chemistry*


  • Antitoxins
  • Bacterial Toxins

Associated data

  • PDB/1GVN