Nikita G. Yabbarov, Elena D. Nikolskaya, Sergei B. Bibikov, Aleksandr A. Maltsev, Margarita V. Chirkina, Mariia R. Mollaeva, Maria B. Sokol, Ekaterina Yu. Epova, Ruslan O. Aliev, Ilya N. Kurochkin
{"title":"Methods for Rapid Evaluation of Microbial Antibiotics Resistance","authors":"Nikita G. Yabbarov, Elena D. Nikolskaya, Sergei B. Bibikov, Aleksandr A. Maltsev, Margarita V. Chirkina, Mariia R. Mollaeva, Maria B. Sokol, Ekaterina Yu. Epova, Ruslan O. Aliev, Ilya N. Kurochkin","doi":"10.1134/S0006297924603678","DOIUrl":"10.1134/S0006297924603678","url":null,"abstract":"<p>Antibiotic resistance is a major challenge for public health systems worldwide. Rapid and effective identification of bacterial strains is critical for reducing the use of antibiotics and restricting the spread of antibiotic-resistant microorganisms. Various approaches have been developed in recent years for rapid bacterial identification and antibiotic susceptibility testing (AST), such as Raman spectroscopy, single cell image analysis, microfluidic techniques, mass spectrometry analysis, use of high-sensitive luminescent and fluorescent tags, impedance-based detection, and others. This review describes the methods developed for rapid bacterial identification and assessment of their antibiotic susceptibility, including general principles, specific problems, and future prospects.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S312 - S341"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Serine-Threonine Protein Kinases of Cyanobacteria","authors":"Anna A. Zorina, Dmitry A. Los, Oleg I. Klychnikov","doi":"10.1134/S0006297924604507","DOIUrl":"10.1134/S0006297924604507","url":null,"abstract":"<p>Protein phosphorylation is a pivotal mechanism for signal transduction, regulation of biochemical processes essential for reproduction, growth, and adaptation of organisms to changing conditions. Bacteria, which emerged more than 3.5 billion years ago, faced the need to adapt to a variety of ecological niches from the very beginning of their existence. It is not surprising that they developed a wide range of different types of kinases and target amino acid residues for phosphorylation. To date, many examples of phosphorylation of serine, threonine, tyrosine, histidine, arginine, lysine, aspartate, and cysteine have been discovered. Bacterial histidine kinases as part of two-component systems have been studied in most detail. More recently eukaryotic type serine-threonine and tyrosine kinases based on the conserved catalytic domain have been described in the genomes of many bacteria. The term “eukaryotic” is misleading, since evolutionary origin of these enzymes goes back to the last common universal ancestor – LUCA. Bioinformatics, molecular genetics, omics, and biochemical strategies combined provide new tools for researchers to establish relationship between the kinase abundance/activity and proteome changes, including studying of the kinase signaling network (kinome) within the cell. This manuscript presents several approaches to investigation of the serine-threonine protein kinases of cyanobacteria, as well as their combination, which allow to suggest new hypotheses and strategies for researchers.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S287 - S311"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Yu. Rudenko, Sofia S. Mariasina, Ratislav M. Ozhiganov, Petr V. Sergiev, Vladimir I. Polshakov
{"title":"Enzymatic Reactions of S-Adenosyl-L-Methionine: Synthesis and Applications","authors":"Alexander Yu. Rudenko, Sofia S. Mariasina, Ratislav M. Ozhiganov, Petr V. Sergiev, Vladimir I. Polshakov","doi":"10.1134/S0006297924604210","DOIUrl":"10.1134/S0006297924604210","url":null,"abstract":"<p><i>S</i>-adenosyl-<i>L</i>-methionine (SAM, AdoMet) is a ubiquitous biomolecule present in all living organisms, playing a central role in a wide array of biochemical reactions and intracellular regulatory pathways. It is the second most common participant in enzymatic reactions in living systems, following adenosine triphosphate (ATP). This review provides a comprehensive analysis of enzymatic reactions involving SAM, whether as a product, a reactant (cosubstrate), or as a non-consumable enzyme cofactor. The discussion encompasses various methods for SAM synthesis, including biotechnological, chemical, and enzymatic approaches. Particular emphasis is placed on the biochemical reactions where SAM functions as a cosubstrate, notably in trans-alkylation reactions, where it acts as a key methyl group donor. Beyond methylation, SAM also serves as a precursor for the synthesis of other molecular building blocks, which are explored in a dedicated section. The review also addresses the role of SAM as a non-consumable cofactor in enzymatic processes, highlighting its function as a prosthetic group for certain protein enzymes and its ability to form complexes with ribozymes. In addition, bioorthogonal systems involving SAM analogues are discussed. These systems employ engineered enzyme–cofactor pairs designed to enable highly selective interactions between target SAM analogues and specific enzymes, facilitating precise reactions even in the presence of other SAM-dependent enzymes. The concluding section explores practical applications of SAM analogues, including their use as selective inhibitors in clinical medicine and as components of reporter systems.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S105 - S134"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan S. Kiselev, Natalia M. Baulina, Olga O. Favorova
{"title":"Epigenetic Clock: DNA Methylation as a Marker of Biological Age and Age-Associated Diseases","authors":"Ivan S. Kiselev, Natalia M. Baulina, Olga O. Favorova","doi":"10.1134/S0006297924602843","DOIUrl":"10.1134/S0006297924602843","url":null,"abstract":"<p>Age is one of the key criteria of human health used in practical medicine to predict the risk of common chronic diseases. However, biological age, which reflects the state of an individual organism, functional capabilities, social well-being, and risk of premature death from various causes, often does not coincide with chronological age. To determine biological age of a particular individuals and the rate of their aging, specific panels of DNA methylation markers called “epigenetic clock” (EC) were proposed. This review summarizes the data about the main types of ECs developed to date and their key characteristics. We described the results of works studying individual aging rates in common age-associated diseases and outlined main directions, development of which could expand application of ECs in fundamental and practical medicine. There is no doubt that revealing complex mechanisms underlying interaction between the rate of epigenetic aging and the risk of age-associated diseases could play a key role for prediction and early diagnosis, as well as for the development of preventive measures that could delay onset of the disease.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S356 - S372"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune Response and Production of Abzymes in Patients with Autoimmune and Neurodegenerative Diseases","authors":"Georgy A. Nevinsky","doi":"10.1134/S0006297924604167","DOIUrl":"10.1134/S0006297924604167","url":null,"abstract":"<p>The mechanisms of development of autoimmune, neurological, and viral diseases and the possibilities of immune response to various antigens in these pathologies still pose many questions. Human immune system is theoretically capable of synthesizing about a million antibodies with very different properties against the same antigen. It remains unclear how many antibodies and with what properties can form in healthy people and patients with autoimmune diseases (AIDs). The capabilities of traditional approaches, such as enzyme immunoassay or affinity chromatography of Abs on specific sorbents, in answering these questions and analyzing the diversity of antibodies formed against external and internal antigens, as well as their role in the pathogenesis of various diseases, are very limited. Analysis of monoclonal antibodies in the blood of patients with systemic lupus erythematosus (SLE) using phage display revealed that the number of autoantibodies against DNA and myelin basic protein (MBP) can exceed 3-4 thousand, and approximately 30-40% of them are abzymes capable of hydrolyzing DNA and MBP. However, this approach does not allow to investigate the variety of properties of such antibodies, in particular their catalytic activity. Abzymes can play either positive or negative role in the development of various diseases. For example, in HIV-infected patients, abzymes against viral polymerase and integrase cleave these proteins, thus slowing down the development of immunodeficiency syndrome. Other antibodies play a negative role in the pathogenesis of viral, neurological, and autoimmune diseases. Thus, antibodies capable of hydrolyzing DNA and histones can penetrate through the cellular and nuclear membranes, stimulate cell apoptosis, and, as a result, trigger autoimmune processes in many pathologies. Antibodies against MBP cleave this protein in the membranes of cells in nerve tissues, leading to the development of multiple sclerosis (MS). In this case, abzymes against individual histones were able to hydrolyze each of these histones, as well as MBP, while Abs against MBP hydrolyzed MBP and all five histones. It has also been established that the substrate specificity of abzymes in the hydrolysis of histones and MBP varied greatly depending on the stage of MS or SLE development. Here, we used this example to analyze in detail the role that abzymes against various antigens play in their expanded involvement in the pathogenesis of some AIDs. The review also describes the impact of defects in the bone marrow stem cell differentiation characteristic of AIDs in the formation of B lymphocytes producing harmful abzymes and summarizes for the first time the data on the exceptional diversity of autoantibodies and abzymes, their unusual biological functions, and involvement in the pathogenesis of autoimmune pathologies.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S373 - S400"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Big, Mysterious World of Plant 14-3-3 Proteins","authors":"Ilya A. Sedlov, Nikolai N. Sluchanko","doi":"10.1134/S0006297924603319","DOIUrl":"10.1134/S0006297924603319","url":null,"abstract":"<p>14-3-3 is a family of small regulatory proteins found exclusively in eukaryotic organisms. They selectively bind to phosphorylated molecules of partner proteins and regulate their functions. 14-3-3 proteins were first characterized in the mammalian brain approximately 60 years ago and then found in plants, 30 years later. The multifunctionality of 14-3-3 proteins is exemplified by their involvement in coordination of protein kinase cascades in animal brain and regulation of flowering, growth, metabolism, and immunity in plants. Despite extensive studies of this diverse and complex world of plant 14-3-3 proteins, our understanding of functions of these enigmatic molecules is fragmentary and unsystematic. The results of studies are often contradictory and many questions remain unanswered, including biochemical properties of 14-3-3 isoforms, structure of protein–protein complexes, and direct mechanisms by which 14-3-3 proteins influence the functions of their partners in plants. Although many plant genes coding for 14-3-3 proteins have been identified, the isoforms for <i>in vivo</i> and <i>in vitro</i> studies are often selected at random. This rather limited approach is partly due to an exceptionally large number and variety of 14-3-3 homologs in plants and erroneous <i>a</i> <i>priori</i> assumptions on the equivalence of certain isoforms. The accumulated results provide an extensive but rather fragmentary picture, which poses serious challenges for making global generalizations. This review is aimed to demonstrate the diversity and scope of studies of the functions of plant 14-3-3 proteins, as well as to identify areas that require further systematic investigation and close scientific attention.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S1 - S35"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viktoriya V. Kolesnikova, Oleg S. Nikonov, Phat Tien Do, Ekaterina Yu. Nikonova
{"title":"The Proteins Diversity of the eIF4E Family in the eIF4F Complex","authors":"Viktoriya V. Kolesnikova, Oleg S. Nikonov, Phat Tien Do, Ekaterina Yu. Nikonova","doi":"10.1134/S0006297924603721","DOIUrl":"10.1134/S0006297924603721","url":null,"abstract":"<p>In eukaryotes, translation initiation occurs by the cap-dependent mechanism. Each translated mRNA must be pre-bound by the translation initiation factor eIF4E. All isoforms of this factor are combined into one family. The review considers natural diversity of the eIF4E isoforms in different organisms, provides structural information about them, and describes their functional role in the processes, such as oncogenesis, participation in the translation of certain mRNAs under stress, and selective use of the individual isoforms by viruses. In addition, this review briefly describes the mechanism of cap-dependent translation initiation and possible ways to regulate the eIF4E function.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1 supplement","pages":"S60 - S85"},"PeriodicalIF":2.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of β- and α-Structures of Membrane Proteins in Plasmalemma Structure Change","authors":"Pavel V. Mokrushnikov, Valery Ya. Rudyak","doi":"10.1134/S0006297924602569","DOIUrl":"10.1134/S0006297924602569","url":null,"abstract":"<p>Changes in the structure of plasma membranes affect functions of membranes and cells. Some of these changes could lead to the development of pathologies in an organism, which makes it important to study effects of the changes in the structure of membranes on their functions. It is considered established at present that when stress hormones and androgens interact with plasma membranes, their structure changes. In the process, interactions between proteins and lipids change in plasmalemmas, and a rigid quasi-periodic network of protein–lipid domains associated with cytoskeleton is formed. Initiators of formation of protein–lipid domains are membrane proteins, which change their secondary structure during interaction of the membrane with hormones. However, it is still unclear exactly what changes in the secondary structure of membrane proteins contribute to formation of the protein–lipid domains around them. The aim of this work was to identify these secondary structures in membrane proteins. To achieve this goal, changes in the structure of membranes during their interaction with dehydroepiandrosterone, cortisol, androsterone, testosterone, and adrenaline were studied. In this work, a fluorescent method for measuring relative microviscosity of membranes using pyrene probe was used to study changes in the membrane structure. Change in the secondary structure of membrane proteins during structural transitions in the membranes was studied by measuring IR absorption spectra of the membranes. It has been established that initiators of the emergence of protein–lipid domains in the plasma membranes are membrane proteins, in which, proportion of the β-structures increases after interaction with hormones. At the same time, appearance of new α-helices in the membrane proteins does not enhance affinity between the membrane proteins, and protein–lipid domains are not formed. On the contrary, appearance of a large number of α-helices in the membrane proteins could lead to the decrease in microviscosity of the lipid bilayer.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1","pages":"79 - 98"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Colocalization of Neurotransmitters in Hippocampus and Afferent Systems: Possible Functional Role","authors":"Valentina F. Kitchigina","doi":"10.1134/S0006297924603915","DOIUrl":"10.1134/S0006297924603915","url":null,"abstract":"<p>In neurophysiology, the transmitter phenotype is considered as an indicator of neuronal identity. It has become known at the end of last century that a nerve cell can produce and use several different molecules to communicate with other neurons. These could be “classical” transmitters: glutamate or gamma-aminobutyric acid (or acetylcholine, serotonin, norepinephrine), as well as secondary messengers, mainly neuropeptides released from the same neurons. In the case, when classical neurotransmitters are released together from the same nerve cell, this event is called cotransmission or corelease (release from the same vesicles). In this review article, the term “cotransmission” is used in a broad sense, denoting neurons that can release more than one classical mediator. Since transmitters are often intermediate products of metabolism and are found in many cells, the neuron classification is currently based on the carrier proteins (transporters) that “pack” neurotransmitters synthesized in the cytoplasm into vesicles. Here, we limit the issue of colocalization of the main neurotransmitters in mammals to the neurons of hippocampus and those structures that send their pathways to it. The review considers problems concerning the mechanisms of multitransmitter signaling, as well as probable functional role of mediator colocalization in the work of hippocampus, which yet has been poorly understood. It has been suggested that co-expression of different mediator phenotypes is involved in maintaining the balance of excitation and inhibition in different regions of hippocampus, facilitates rapid selection of information processing mode, induction of long-term potentiation, maintenance of spatial coding by place cells, as well as ensuring flexibility of learning and formation of working memory. However, the functional role of mediator colocalization, as well as the mechanisms of release of “dual” transmitters, have not been fully elucidated. The solution of these problems will advance some areas of fundamental neuroscience and help in the treatment of those diseases, where disruption of the balance between excitation and inhibition is detected, such as, for example, in epilepsy, Alzheimer’s disease, and many others.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1","pages":"61 - 78"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tatiana S. Usenko, Katerina S. Basharova, Anastasia I. Bezrukova, Vadim A. Bezrukikh, Galina V. Baydakova, Ekaterina Yu. Zakharova, Sofya N. Pchelina
{"title":"Effect of LRRK2 Inhibition on the Activity of Glucocerebrosidase in Patient-Specific Cells from Patients with Gaucher Disease","authors":"Tatiana S. Usenko, Katerina S. Basharova, Anastasia I. Bezrukova, Vadim A. Bezrukikh, Galina V. Baydakova, Ekaterina Yu. Zakharova, Sofya N. Pchelina","doi":"10.1134/S0006297924602739","DOIUrl":"10.1134/S0006297924602739","url":null,"abstract":"<p>Biallelic mutations in the <i>GBA1</i> gene encoding lysosomal enzyme glucocerebrosidase (GCase), lead to the development of the Gaucher disease (GD) and also represent a significant risk factor for the Parkinson’s disease (PD). In most cases, mutations in the <i>GBA1</i> gene are located outside the region coding for the enzyme active site and cause a decrease in the GCase activity due to the reduction in the efficiency of transport of conformationally altered enzyme to the lysosomes. Drugs used to treat GD (enzyme replacement therapy) cannot cross the blood-brain barrier and, therefore, are not effective in the treatment of neuronal forms of GD or PD associated with mutations in the <i>GBA1</i> gene (GBA1-PD). Currently, inhibitors of the leucine-rich repeat kinase 2 (LRRK2) are undergoing clinical trials for the treatment of PD. It was previously shown that inhibition of LRRK2 leads to the increase in the GCase activity in patient-specific GBA1-PD cells. We assessed the effect of the LRRK2 inhibitor MLi-2 on the GCase activity in the primary culture of peripheral blood macrophages from patients with type 1 GD. The activity of GCase and the levels of its substrate in cells cultured with and without MLi-2 was assayed by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). No effect of LRRK2 inhibition on the activity GCase in a group of patients with GD was found.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":"90 1","pages":"99 - 106"},"PeriodicalIF":2.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143570896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}