2P5T

Molecular and structural characterization of the PezAT chromosomal toxin-antitoxin system of the human pathogen Streptococcus pneumoniae

Summary for 2P5T

• Entry DOI: 10.2210/pdb2p5t/pdb
• Related: 1GVN
• Descriptor: fragment of PezA helix-turn-helix motif, Putative transcriptional regulator PezA, PezT (3 entities in total)
• Functional Keywords: postsegregational killing system, phosphoryltransferase, helix-turn-helix motif, transcription regulator
• Biological source: Streptococcus pneumoniae; More
• Total number of polymer chains: 9
• Total formula weight: 192321.52

Authors

Loll, B.,Meinhart, A. (deposition date: 2007-03-16, release date: 2007-05-15, Last modification date: 2024-02-21)

Primary citation

Khoo, S.K.,Loll, B.,Chan, W.T.,Shoeman, R.L.,Ngoo, L.,Yeo, C.C.,Meinhart, A.
Molecular and Structural Characterization of the PezAT Chromosomal Toxin-Antitoxin System of the Human Pathogen Streptococcus pneumoniae.
J.Biol.Chem., 282:19606-19618, 2007

PubMed 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.

PubMed: 17488720
DOI: 10.1074/jbc.M701703200

Experimental method

X-RAY DIFFRACTION (3.2 Å)