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Type II Toxin-Antitoxin loci: The phd/doc Family Vrije Universiteit Brussel
The phd/doc family is one the smallest families of toxin-antitoxin modules and was first discovered as a plasmid addiction module on E. coli bacteriophage P1. The toxin Doc interacts with the ribosome, competes with hygromycin and inhibits translation. Structurally, Doc resembles Fic domains, which are known to transfer an AMP moiety to the hydroxyphenyl group of a tyrosine in the target protein. Although much of the AMP/ATP binding site of Fic ...
The ParE2-PaaA2 toxin-antitoxin complex from E. coli O157 forms a hetero-docecamer in solution and in the crystal Vrije Universiteit Brussel
The Escherichia coli O157 paaR2-paaA2-parE2 constitutes a unique three-component toxin-antitoxin (TA) module with a toxin (ParE2) related to the classic parDE family, but with an unrelated antitoxin called PaaA2. The complex between PaaA2 and ParE2 was purified and characterized by analytical gel filtration, dynamic light scattering, and small-angle X-ray scattering. It consists of a particle with a radius of gyration of 3.95 nm and likely forms ...
Crystallization of the HigBA2 toxin-antitoxin complex from Vibrio cholerae. Vrije Universiteit Brussel
The genome of Vibrio cholerae encodes two higBA toxin-antitoxin (TA) modules that are activated by amino-acid starvation. Here, the TA complex of the second module, higBA2, as well as the C-terminal domain of the
corresponding HigA2 antitoxin, have been purified and crystallized. The HigBA2 complex crystallized in two crystal forms. Crystals of form I belonged to space group P21212, with unit-cell parameters a = 129.0, b = 119.8, c = 33.4 ...
corresponding HigA2 antitoxin, have been purified and crystallized. The HigBA2 complex crystallized in two crystal forms. Crystals of form I belonged to space group P21212, with unit-cell parameters a = 129.0, b = 119.8, c = 33.4 ...
New bactericidal toxins homologous to ParE belonging to 3-component toxin-antitoxin systems in Escherichia coli O157:H7. Vrije Universiteit Brussel
Type II toxin-antitoxin (TA) systems are considered as protein pairs in which a specific toxin is associated with a specific antitoxin. We have identified a novel antitoxin family (paaA) that is associated with parE toxins. The paaA-parE gene pairs form an operon with a third component (paaR) encoding a transcriptional regulator. Two paralogous paaR-paaA-parE systems are found in E. coli O157:H7. Deletions of the paaA-parE pairs in O157:H7 ...
Crystallization of Doc and the Phd:Doc toxin-antitoxin complex Vrije Universiteit Brussel
The phd/doc addiction system is responsible for the stable inheritance of lysogenic bacteriophage P1 in its plasmidic form in Escherichia coli and is the archetype of a family of bacterial toxin-antitoxin modules. The His66Tyr mutant of Doc (DocH66Y) was crystallized in space group P21, with unit-cell parameters a = 53.1 A, b = 198.0 A, c = 54.1 A, beta = 93.0°. These crystals diffract to 2.5 A resolution and probably contain four dimers of Doc ...
Crystallization and preliminary X-ray analysis of two variants of the Escherichia coli O157 ParE2-PaaA2 toxin-antitoxin complex University of Antwerp
The paaR2-paaA2-parE2 operon is a three-component toxin-antitoxin module encoded in the genome of the human pathogen Escherichia coli O157. The toxin (ParE2) and antitoxin (PaaA2) interact to form a nontoxic toxin-antitoxin complex. In this paper, the crystallization and preliminary characterization of two variants of the ParE2-PaaA2 toxin-antitoxin complex are described. Selenomethionine-derivative crystals of the full-length ParE2-PaaA2 ...
The ParE2-PaaA2 toxin-antitoxin complex from Escherichia coli O157 forms a heterodocecamer in solution and in the crystal University of Antwerp
Escherichia coli O157 paaR2-paaA2-parE2 constitutes a unique three-component toxinantitoxin (TA) module encoding a toxin (ParE2) related to the classic parDE family but with an unrelated antitoxin called PaaA2. The complex between PaaA2 and ParE2 was purified and characterized by analytical gel filtration, dynamic light scattering and small-angle X-ray scattering. It consists of a particle with a radius of gyration of 3.95 nm and is likely to ...
Computational Methods to Model Persistence Vrije Universiteit Brussel
Bacterial persister cells are dormant cells, tolerant to multiple antibiotics, that are involved in several chronic infections. Toxin–antitoxin modules play a significant role in the generation of such persister cells. Toxin–antitoxin modules are small genetic elements, omnipresent in the genomes of bacteria, which code for an intracellular toxin and its neutralizing antitoxin. In the past decade, mathematical modeling has become an important ...
Structural and biophysical characterization of Staphylococcus aureus SaMazF shows conservation of functional dynamics. Vrije Universiteit Brussel
The Staphylococcus aureus genome contains three toxin-antitoxin modules, including one mazEF module, SamazEF. Using an on-column separation protocol we are able to obtain large amounts of wild-type SaMazF toxin. The protein is well-folded and highly resistant against thermal unfolding but aggregates at elevated temperatures. Crystallographic and nuclear magnetic resonance (NMR) solution studies show a well-defined dimer. Differences in structure ...