Institute of
bioorganic chemistry

Сascade synthesis of arabinosides is a promising approach for the production of various important antiviral and cancer suppressing drugs. However, the low activity of the cascades first enzyme - ribokinase towards D-arabinose limits the technological feasibility of this approach. Researchers from the lab. of Biopharmaceutical Technologies and lab. of Biosynthesis of Physiologically Active Compounds from the dep. of Biotechnology of IBCh RAS have performed the rational design in the active site of ribokinase from E. coli, resulting in a 15-fold increase in enzyme activity (k cat ) towards D-arabinose through the A98G mutation. The engineered mutant has allowed to decrease the consumption of this enzyme by an order of magnitude with no loss in the efficiency of synthesis of the model arabinoside. The results were published in International Journal of Molecular Sciences (IF=6.208, Q1).

A team of scientists from the Department of Biotechnology of IBCh in collaboration with colleagues from ITHT-RTU-MIREA synthesized a series of 5-alkyl/aryl-hydroxymethyl- ribavirin analogs. Ribonucleosides were synthesized by classical chemical glycosylation, while 2'-deoxyribonucleosides were synthesized by transglycosylation with E. coli PNP. When studying the kinetic parameters, a positive cooperative effect of PNP active sites was discovered for the first time. Nucleosides were active against herpes simplex virus type 1 (HSV-1) and influenza virus H5N1. The work was published in the journal Sustainable Chemistry and Pharmacy (IF 5.464, Q2).

In the study of ATP-dependent Lon proteases – key members of the cellular proteome quality control system, scientists from the Laboratory of Proteolytic Enzyme Chemistry of IBСh RAS in collaboration with colleagues from the National Cancer Institute (Frederick, USA) revealed a group of enzymes that bear structural features of participants of both previously studied basic LonA and LonB subfamilies. These enzymes were proposed to consider as a new "hybrid" LonBA subfamily. The protease (P) domain of LonBAs has a unique among Lon family fold as it was shown by 3D analysis of the enzyme from Bacillus subtilis (BsLonBA). The experimentally solved P domain structure was combined with the structure of the BsLonBA ATPase component modeled using the AlphaFold2 program. The predicted structure of full- length BsLonBA was compared with the known structures of LonA and LonB proteases. Possible peculiarities of the LonBA proteases functioning are discussed. The work was published in the International Journal of Molecular Sciences.

Persistence of B cell clones and fine-tuning of their BCRs allow them to respond effectively to repeated immune challenges. Researchers from the Genomics of adaptive immunity department of IBCH in collaboration with colleagues from IITP and Skoltech, performed long-term study of structure and dynamics of BCR repertoire of memory B cells and antibody-secreting cells from peripheral blood of healthy donors. Memory B cell BCR repertoire have distinctive features, relatively stable over time and largely unique to independent donors. Phylogenetic approach for BCR repertoire analysis showed evidence of positive and negative selection affecting affinity maturation after reactivation as well as protection of BCR functionality and antigen- specificity persisting memory clones. The study published in eLife.

Tools created at the Laboratory of Biomolecular Modelling IBCh RAS have been brought together into a computational framework to build a model of SARS-CoV-2 spike transmembrane domain (TMD). Apart from template-based modelling, the framework relies on the molecular hydrophobicity potential (MHP) analyser Platinum, dimer prediction utility PREDDIMER and the adjustment of ‘dynamic MHP portraits’ observed during molecular dynamics simulations. The final model, the only existing one taking into account the lipid environment and helical TMD packing principles, demonstrated phenomenal stability in a model membrane, both on its own and palmitoylated downstream, proving to be stabler than alternative models and a recent NMR structure. The results are published in the International Journal of Molecular Sciences. Learn more