Our recent review in a BBA Special Issue

Kinga Nyíri and Beáta Vértessy recently published a review in Science for Life Special Issue of BBA General Subjects about the

Perturbation of genome integrity to fight pathogenic microorganisms.

The review summarizes the current advances of thymidylate biosynthesis inhibition in challenging pathogens.

Resistance against antibiotics is unfortunately still a major biomedical challenge for a wide range of pathogens responsible for potentially fatal diseases.

Scope of review
In this study, we aim at providing a critical assessment of the recent advances in design and use of drugs targeting genome integrity by perturbation of thymidylate biosynthesis.

Major conclusion
We find that research efforts from several independent laboratories resulted in chemically highly distinct classes of inhibitors of key enzymes within the routes of thymidylate biosynthesis. The present article covers numerous studies describing perturbation of this metabolic pathway in some of the most challenging pathogens like Mycobacterium tuberculosis, Plasmodium falciparum, and Staphylococcus aureus.

General significance
Our comparative analysis allows a thorough summary of the current approaches to target thymidylate biosynthesis enzymes and also include an outlook suggesting novel ways of inhibitory strategies.

 Nyiri Fig1 Nyiri Fig3



New article published in PLos One

Mária Pukáncsik and Kinga Nagy article is published in PLos One.

Hereby you may find some highlights making you eager to read this very interesting article.

A novel uracil-DNA degrading protein factor (termed UDE) was identified in Drosophila melanogaster with no significant structural and functional homology to other uracil-DNA binding or processing factors. Determination of the 3D structure of UDE is excepted to provide key information on the description of the molecular mechanism of action of UDE catalysis, as well as in general uracil-recognition and nuclease action. Towards this long-term aim, the random library ESPRIT technology was applied to the novel protein UDE to overcome problems in identifying soluble expressing constructs given the absence of precise information on domain content and arrangement. Nine constructs of UDE were chosen to decipher structural and functional relationships. Vacuum ultraviolet circular dichroism (VUVCD) spectroscopy was performed to define the secondary structure content and location within UDE and its truncated variants. The quantitative analysis demonstrated exclusive α-helical content for the full-length protein, which is preserved in the truncated constructs. Arrangement of α-helical bundles within the truncated protein segments suggested new domain boundaries which differ from the conserved motifs determined by sequence-based alignment of UDE homologues. Here we demonstrate that the combination of ESPRIT and VUVCD spectroscopy provides a new structural description of UDE and confirms that the truncated constructs are useful for further detailed functional studies.

nagy kinga cikk jo

A) Secondary structure content determination of UDE and its fragments using VUVCD and SELCON3 program. Vacuum-ultraviolet circular dichroism (Δε) spectra of the UDE protein and some of its truncated fragments measured over the wavelength region of λ=170-255 nm. spectrum of UDE is shown in red. B) Final estimate for the secondary structure of UDE obtained as an average of the structure of full-length UDE protein and in its nine truncated fragments were determined from the CD spectra and the amino acid sequence using a neural network algorithm. The α-helical segments and β-strands are displayed in blue and red, respectively, while both turns and disordered parts appear in yellow.


Genome Metabolism and Biostruct Laboratory

Budapest University of Technology, Ch building
Szt. Gellért square 4.

RCNS Institute of Enzymology
Magyar tudosok korutja 2.