A5033744508- Enzyme Catalysis and Immobilization
- Chemical Synthesis and Analysis
- Protein Structure and Dynamics
- Enzyme Structure and Function
- Carbohydrate Chemistry and Synthesis
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Microbial Metabolic Engineering and Bioproduction
- Analytical Chemistry and Chromatography
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- DNA Repair Mechanisms
- Computational Drug Discovery Methods
- Amino Acid Enzymes and Metabolism
- Genomics and Phylogenetic Studies
- Influenza Virus Research Studies
- Fluorine in Organic Chemistry
- Antibiotics Pharmacokinetics and Efficacy
- HIV/AIDS drug development and treatment
- Cancer therapeutics and mechanisms
- Protein Interaction Studies and Fluorescence Analysis
- Toxin Mechanisms and Immunotoxins
Lomonosov Moscow State University
2015-2024
Moscow State University
2011-2024
Institute of Mathematical Problems of Biology
2021-2023
Computing Center
2023
Bioengineering Center
2019
University of Trieste
2012
Delft University of Technology
2008
Physico-Technical Institute
1998
Institute of Bioorganic Chemistry and Petrochemistry V.P. Kukhar
1993-1996
Université de Montréal
1996
Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a repair enzyme for stalled DNA-topoisomerase (Top1) cleavage complexes and other 3'-end DNA lesions. TDP1 perspective target anticancer therapy based on Top1-poison-mediated damage. Several novel usnic acid derivatives with an enamine moiety have been synthesized tested as inhibitors of TDP1. The enamines showed IC50 values in the range 0.16 to 2.0 μM. These compounds revealed moderate cytotoxicity against human tumor MCF-7 cells. new enhanced...
Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein is important study structure-function relationship design functions. Thermal has been extensively studied connection with practical application biocatalysts. However, little work done explore mechanism pH-dependent inactivation. In this study,...
Superfamily of alpha-beta hydrolases is one the largest groups structurally related enzymes with diverse catalytic functions. Bioinformatic analysis was used to study how lipase and amidase activities are implemented into same structural framework. Subfamily-specific positions—conserved within lipases peptidases but different between them—that were supposed be responsible for functional discrimination have been identified. Mutations at subfamily-specific positions introduce activity Candida...
Biomimetic transamination of the commercially available ethyl 2-methyl-3-keto-4,4,4-trifluorobutyrate (4) with benzylamine was shown to provide a simple access 2-methyl-3-amino-4,4,4-trifluorobutanoic acids, hitherto unknown biologically relevant β-amino acid. In sharp contrast α-unsubstituted β-keto carboxylic esters α-methyl ester 4 proceeds under mild reaction conditions, presumably, due relative instability intermediate (Z)-enamine 6. Diastereoselectivity process found be controlled by...
During evolution of proteins from a common ancestor, one functional property can be preserved while others vary leading to diversity. A systematic study the corresponding adaptive mutations provides key most challenging problems modern structural biology – understanding impact amino acid substitutions on protein function. The subfamily-specific positions (SSPs) are conserved within subfamilies but different between them and, therefore, seem responsible for diversity in superfamilies....
Understanding the role of specific amino acid residues in molecular mechanism a protein's function is one most challenging problems modern biology. A systematic bioinformatic analysis protein families and superfamilies can help study structure–function relationships design improved variants enzymes/proteins, but represents methodological challenge. The pyridoxal‐5′‐phosphate ( PLP )‐dependent enzymes are catalytically diverse include aspartate aminotransferase superfamily which implements...
7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as potential anticancer drug candidate. Here we describe study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 nucleosomal DNA. It is shown competes with substrate NAD+ its binding in...
The PARP family consists of 17 members with diverse functions, including those related to cancer cells’ viability. Several inhibitors are great interest as innovative anticancer drugs, but they have low selectivity towards distinct and exert serious adverse effects. We describe a family-wide study the nicotinamide (NA) binding site, an important functional region in structure, using comparative bioinformatic analysis molecular modeling. Mutations NA site D-loop mobility around were...
Penicillin acylase from Alcaligenes faecalis has a very high affinity for both natural (benzylpenicillin, K m =0.0042 mM) and colorimetric (6‐nitro‐3‐phenylacetamidobenzoic acid, =0.0045 substrates as well the product of their hydrolysis, phenylacetic acid ( i =0.016 mM). The enzyme is partially inhibited at benzylpenicillin concentrations but triple SES complex formed still retains 43% maximal catalytic activity; second substrate molecule binding site much lower S ′=54 than first one....
Abstract The synthesis of ampicillin catalyzed by Escherichia coli penicillin acylase was optimized in an aqueous system with partially dissolved antibiotic nucleus 6‐aminopenicillanic acid (6‐APA). yields both 6‐APA and acyl donor could be improved repetitively adding substrates to the reaction, allowing concentration remain saturated throughout. In this reaction concept, four subsequent additions substrates, 97% conversion 72% D ‐(−)‐phenylglycine methyl ester (D‐PGM) achieved. synthetic...
Abstract Native and immobilized preparations of penicillin acylase from Escherichia coli Alcaligenes faecalis were studied using an active site titration technique. Knowledge the number sites allowed calculation average turnover rate enzyme in various us to quantify contribution irreversible inactivation loss catalytic activity during immobilization procedure. In most cases a as well decrease per (turnover rate) was observed upon immobilization. Immobilization techniques affected enzymes...