2P5T: Molecular And Structural Characterization Of The Pezat Chromosomal Toxin-Antitoxin System Of The Human Pathogen Streptococcus Pneumoniae

Citation:
Abstract
The chromosomal pezT gene of the Gram-positive pathogen Streptococcus pneumoniae encodes a protein that is homologous to the zeta toxin of the Streptococcus pyogenes plasmid pSM19035-encoded epsilon-zeta toxin-antitoxin system. Overexpression of pezT in Escherichia coli led to severe growth inhibition from which the bacteria recovered approximately 3 h after induction of expression. The toxicity of PezT was counteracted by PezA, which is encoded immediately upstream of pezT and shares weak sequence similarities in the C-terminal region with the epsilon antitoxin. The pezAT genes form a bicistronic operon that is co-transcribed from a sigma(70)-like promoter upstream of pezA and is negatively autoregulated with PezA functioning as a transcriptional repressor and PezT as a co-repressor. Both PezA and the non-toxic PezA(2)PezT(2) protein complex bind to a palindrome sequence that overlaps the promoter. This differs from the epsilon-zeta system in which epsilon functions solely as the antitoxin and transcriptional regulation is carried out by another protein designated omega. Results from site-directed mutagenesis experiments demonstrated that the toxicity of PezT is dependent on a highly conserved phosphoryltransferase active site and an ATP/GTP nucleotide binding site. In the PezA(2)PezT(2) complex, PezA neutralizes the toxicity of PezT by blocking the nucleotide binding site through steric hindrance.
PDB ID: 2P5TDownload
MMDB ID: 46504
PDB Deposition Date: 2007/3/16
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 3.2  Å
Source Organism:
Streptococcus pneumoniae TIGR4
Similar Structures:
Biological Unit for 2P5T: tetrameric; determined by author and by software (PISA)
Molecular Components in 2P5T
Label Count Molecule
Proteins (4 molecules)
2
Putative Transcriptional Regulator Peza
Molecule annotation
2
Pezt
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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