[Factors Affecting the Stability of the Trimer of 2'-Deoxyuridine 5'-Triphosphate Nucleotide Hydrolase from Escherichia coli].

2'-Deoxyuridine 5'-triphosphate nucleotide hydrolase (Dut) hydrolyzes dUTP to dUMP and pyrophosphate to prevent erroneous incorporation of dUMP from the dUTP metabolic pool into DNA. Dut is considered as a promising pharmacological target for antimetabolite therapy. Enzymatically active Dut is a trimer that binds the substrate at the interface between the subunits. High-speed nanoscale differential scanning fluorimetry (nanoDSF) was used to study how various physicochemical factors affect the stability of the Escherichia coli Dut trimer. Unlike with monomeric proteins, thermal unfolding of Dut occurred in two steps, the first one corresponding to dissociation of the trimer into monomeric subunits. Hydrophobic interactions and hydrogen bonds at the interfaces between the subunits were found to contribute most to trimer stabilization. The binding of nucleotide ligands partly stabilized the Dut trimer. In general, nanoDSF is a convenient assay for screening low-molecular-weight compounds for their ability to destabilize the active Dut trimer.

[On the development of a system of medical weather forecast for the Caucasian Mineral Waters spa-and-resort complex].

A system of medical weather forecast for the Caucasian Mineral Waters spa-and-resort complex has been modified and updated based on the results of long-term observations of weather conditions in the region of interest with special reference to the bioclimatic regime, atmospheric circulation, aerosol pollution of the near-ground air, ultraviolet radiation, heliomagnetic activity, and meteopathic effects. This system provides a basis for the timely emergency meteopreventive treatment of meteodependent patients and therefore can be instrumental in enhancing efficiency of spa-and-resort rehabilitative therapy.