Institute of
bioorganic chemistry

The researchers from the IBCh RAS together with the collaborators from the Institute of Cytology RAS demonstrated for the first time the expression of functionally active ASIC1a channels in U251 MG and A172 gliomas cells, but not in normal astrocytes. A recombinant analogue of mambalgin-2 from black mamba venom was used to suppress the cation influx through ASIC1a channels in glioma cells. As it turned out, mambalgin-2 inhibits the growth of gliomas with EC 50 in the nanomolar range, while not affecting the proliferation of normal astrocytes. Mutant variants of mambalgin-2 with impaired affinity for ASIC1a did not affect the proliferation of glioma cells. It was shown that the decrease in the growth of gliomas cells using mambalgin-2 is associated with the cell cycle arrest, inhibition of phosphorylation of cyclin D1 and cyclin-dependent kinases, and apoptosis induction. The study was published in the Cancers journal under support of the Russian Foundation for Basic Research. Learn more

Researchers from IBCh RAS together with their international collаborators discovered an evolutionary link between efficiency of start codons and the probability of AUG codon occurrence in the 5'-end parts of protein-coding sequences. When start codons are inefficient the next AUG codon is more likely to be found in the same reading frame. At the same time in case of highly efficient start codons, the next AUG codon is more likely to be found in alternative frames. They also have shown that weak initiation at the first starts is associated with the synthesis of shortened proteoforms as a result of initiation at the second starts. The study was published in the journal Genome Research. Learn more

A collaboration of scientists from the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, the Moscow Institute of Physics and Technology and Prokhorov General Physics Institute of the Russian Academy of Sciences have developed a breakthrough technology to resolve a key problem that has prevented the introduction of novel drugs into clinical practice for decades. The new solution prolongs blood circulation for virtually any nanomedicine, boosting its therapeutic efficiency. The study was published in Nature Biomedical Engineering and featured in the journal’s News & Views section. Learn more

Kinase-mediated phosphorylation represents one of the general strategies for the emergence of antibiotic resistance. Scientists from the Laboratory of biocatalysis reported a unique bioscavenging kinase AmiN, member of a new subfamily of AmiN-like kinases, isolated from the Siberian bear microbiome, inactivates antibiotic amicoumacin by phosphorylation. The nanomolar substrate affinity defines AmiN as a phosphotransferase with a unique catalytic efficiency proximal to the diffusion limit. Crystallographic analysis and multiscale simulations revealed a catalytically perfect mechanism providing phosphorylation exclusively in the case of a closed active site that counteracts substrate promiscuity. AmiN kinase is a member of the previously unknown subfamily representing the first evidence of a specialized phosphotransferase bioscavenger. The work is published in Science Advances.

Wood formation is an extremely complex process, controlled by more than 40,000 genes.At the cellular level, wood is nothing but lignified cell walls that constructed from three main structural biopolymers - cellulose, hemicellulose and lignins. The main component of hemicellulose is xyloglucans, which form short cross-links between long cellulose filaments. The more stitches, the lower the elasticity of the cell wall. Scientists from the Group of Forest Biotechnology together with russian and foreign colleages suggested that partial, rather than excessive, hydrolysis of xyloglucans may affect the elasticity of the cell wall, and indirectly the growth rate of the tree. In transgenic models of aspen, they have shown that superexpression of recombinant xyloglucanase from the fungus P.canescens leads not only to hydrolysis of cell wall xyloglucans, but also is accompanied by a complex of changes in the phenotype: the content of cellulose in wood is increased, the carbohydrate composition of wood are changed, as a result, the wood began to decompose more slowly. The work is published in BMC Plant Biology. Learn more