Biochemistry (Moscow)最新文献

{"title":"Role of Mod(mdg4)-67.2 Protein in Interactions between Su(Hw)-Dependent Complexes and Their Recruitment to Chromatin","authors":"Larisa S. Melnikova,&nbsp;Varvara V. Molodina,&nbsp;Pavel G. Georgiev,&nbsp;Anton K. Golovnin","doi":"10.1134/S0006297924040035","DOIUrl":"10.1134/S0006297924040035","url":null,"abstract":"<p>Su(Hw) belongs to the class of proteins that organize chromosome architecture, determine promoter activity, and participate in formation of the boundaries/insulators between the regulatory domains. This protein contains a cluster of 12 zinc fingers of the C2H2 type, some of which are responsible for binding to the consensus site. The Su(Hw) protein forms complex with the Mod(mdg4)-67.2 and the CP190 proteins, where the last one binds to all known <i>Drosophila</i> insulators. To further study functioning of the Su(Hw)-dependent complexes, we used the previously described <i>su(Hw)</i>^E8 mutation with inactive seventh zinc finger, which produces mutant protein that cannot bind to the consensus site. The present work shows that the Su(Hw)^E8 protein continues to directly interact with the CP190 and Mod(mdg4)-67.2 proteins. Through interaction with Mod(mdg4)-67.2, the Su(Hw)^E8 protein can be recruited into the Su(Hw)-dependent complexes formed on chromatin and enhance their insulator activity. Our results demonstrate that the Su(Hw) dependent complexes without bound DNA can be recruited to the Su(Hw) binding sites through the specific protein–protein interactions that are stabilized by Mod(mdg4)-67.2.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886431","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":"Cohesin-Dependent Loop Extrusion: Molecular Mechanics and Role in Cell Physiology","authors":"Arkadiy K. Golov,&nbsp;Alexey A. Gavrilov","doi":"10.1134/S0006297924040023","DOIUrl":"10.1134/S0006297924040023","url":null,"abstract":"<p>The most prominent representatives of multisubunit SMC complexes, cohesin and condensin, are best known as structural components of mitotic chromosomes. It turned out that these complexes, as well as their bacterial homologues, are molecular motors, the ATP-dependent movement of these complexes along DNA threads leads to the formation of DNA loops. In recent years, we have witnessed an avalanche-like accumulation of data on the process of SMC dependent DNA looping, also known as loop extrusion. This review briefly summarizes the current understanding of the place and role of cohesin-dependent extrusion in cell physiology and presents a number of models describing the potential molecular mechanism of extrusion in a most compelling way. We conclude the review with a discussion of how the capacity of cohesin to extrude DNA loops may be mechanistically linked to its involvement in sister chromatid cohesion.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140886517","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 Mechanism of Inhibition of Mycobacterial (p)ppGpp Synthetases by a Synthetic Analog of Erogorgiaene","authors":"Roman Y. Sidorov,&nbsp;Alexander G. Tkachenko","doi":"10.1134/S0006297924030027","DOIUrl":"10.1134/S0006297924030027","url":null,"abstract":"<p>The synthesis of (p)ppGpp alarmones plays a vital role in the regulation of metabolism suppression, growth rate control, virulence, bacterial persistence, and biofilm formation. The (p)ppGpp alarmones are synthesized by proteins of the RelA/SpoT homolog (RSH) superfamily, including long bifunctional RSH proteins and small alarmone synthetases. Here, we investigated enzyme kinetics and dose-dependent enzyme inhibition to elucidate the mechanism of 4-(4,7-dimethyl-1,2,3,4-tetrahydronaphthalen-1-yl)pentanoic acid (DMNP) action on the (p)ppGpp synthetases Rel_Msm and RelZ from <i>Mycolicibacterium smegmatis</i> and Rel_Mtb from <i>Mycobacterium tuberculosis</i>. DMNP was found to inhibit the activity of Rel_Mtb. According to the enzyme kinetics analysis, DMNP acts as a noncompetitive inhibitor of Rel_Msm and RelZ. Based on the results of molecular docking, the DMNP-binding site is located in the proximity of the synthetase domain active site. This study might help in the development of alarmone synthetase inhibitors, which includes relacin and its derivatives, as well as DMNP – a synthetic analog of the marine coral metabolite erogorgiaene. Unlike conventional antibiotics, alarmone synthetase inhibitors target metabolic pathways linked to the bacterial stringent response. Although these pathways are not essential for bacteria, they regulate the development of adaptation mechanisms. Combining conventional antibiotics that target actively growing cells with compounds that impede bacterial adaptation may address challenges associated with antimicrobial resistance and bacterial persistence.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580072","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 Impact of Long-Term Hypoxia on the Antioxidant Defense System in the Siberian Frog Rana amurensis","authors":"Sergei V. Shekhovtsov,&nbsp;Yana L. Vorontsova,&nbsp;Irina A. Slepneva,&nbsp;Dmitry N. Smirnov,&nbsp;Ekaterina E. Khrameeva,&nbsp;Alexey Shatunov,&nbsp;Tatiana V. Poluboyarova,&nbsp;Nina A. Bulakhova,&nbsp;Ekaterina N. Meshcheryakova,&nbsp;Daniil I. Berman,&nbsp;Viktor V. Glupov","doi":"10.1134/S0006297924030052","DOIUrl":"10.1134/S0006297924030052","url":null,"abstract":"<p>The Siberian frog <i>Rana amurensis</i> has a uniquely high tolerance to hypoxia among amphibians, as it is able to withstand several months underwater with almost no oxygen (0.2 mg/liter) vs. several days for other studied species. Since it was hypothesized that hypoxia actives the antioxidant defense system in hypoxia-tolerant animals, one would expect similar response in <i>R.</i> <i>amurensis</i>. Here, we studied the effect of hypoxia in the Siberian frog based on the transcriptomic data, activities of antioxidant enzyme, and content of low-molecular-weight antioxidants. Exposure to hypoxia upregulated expression of three relevant transcripts (catalase in the brain and two aldo-keto reductases in the liver). The activities of peroxidase in the blood and catalase in the liver were significantly increased, while the activity of glutathione S-transferase in the liver was reduced. The content of low-molecular-weight antioxidants (thiols and ascorbate) in the heart and liver was unaffected. In general, only a few components of the antioxidant defense system were affected by hypoxia, while most remained unchanged. Comparison to other hypoxia-tolerant species suggests species-specific adaptations to hypoxia-related ROS stress.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586836","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":"Oxidative Stress-Induced Platelet Apoptosis/Activation: Alleviation by Purified Curcumin via ASK1-JNK/p-38 Pathway","authors":"Kurnegala Manikanta,&nbsp;Manoj Paul,&nbsp;Vaddaragudisalu D. Sandesha,&nbsp;Shanmuga S. Mahalingam,&nbsp;Thimmasandra Narayan Ramesh,&nbsp;Krishnegowda Harishkumar,&nbsp;Shashank S. Koundinya,&nbsp;Shivanna Naveen,&nbsp;Kempaiah Kemparaju,&nbsp;Kesturu S. Girish","doi":"10.1134/S0006297924030039","DOIUrl":"10.1134/S0006297924030039","url":null,"abstract":"<p>Platelets are known for their indispensable role in hemostasis and thrombosis. However, alteration in platelet function due to oxidative stress is known to mediate various health complications, including cardiovascular diseases and other health complications. To date, several synthetic molecules have displayed antiplatelet activity; however, their uses are associated with bleeding and other adverse effects. The commercially available curcumin is generally a mixture of three curcuminoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Although crude curcumin is known to inhibit platelet aggregation, the effect of purified curcumin on platelet apoptosis, activation, and aggregation remains unclear. Therefore, in this study, curcumin was purified from a crude curcumin mixture and the effects of this preparation on the oxidative stress-induced platelet apoptosis and activation was evaluated. 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) compound was used as an inducer of oxidative stress. Purified curcumin restored AAPH-induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cardiolipin peroxidation, cytochrome <i>c</i> release from mitochondria to the cytosol, and phosphatidyl serine externalization. Further, it inhibited the agonist-induced platelet activation and aggregation, demonstrating its antiplatelet activity. Western blot analysis confirms protective effect of the purified curcumin against oxidative stress-induced platelet apoptosis and activation via downregulation of MAPKs protein activation, including ASK1, JNK, and p-38. Together, these results suggest that the purified curcumin could be a potential therapeutic bioactive molecule to treat the oxidative stress-induced platelet activation, apoptosis, and associated complications.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586757","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":"Overexpression of the limk1 Gene in Drosophila melanogaster Can Lead to Suppression of Courtship Memory in Males","authors":"Aleksandr V. Zhuravlev,&nbsp;Oleg V. Vetrovoy,&nbsp;Ekaterina S. Zalomaeva,&nbsp;Ekaterina S. Egozova,&nbsp;Ekaterina A. Nikitina,&nbsp;Elena V. Savvateeva-Popova","doi":"10.1134/S0006297924030015","DOIUrl":"10.1134/S0006297924030015","url":null,"abstract":"<p>Courtship suppression is a behavioral adaptation of the fruit fly. When majority of the females in a fly population are fertilized and non-receptive for mating, a male, after a series of failed attempts, decreases its courtship activity towards all females, saving its energy and reproductive resources. The time of courtship decrease depends on both duration of unsuccessful courtship and genetically determined features of the male nervous system. Thereby, courtship suppression paradigm can be used for studying molecular mechanisms of learning and memory. p-Cofilin, a component of the actin remodeling signaling cascade and product of LIM-kinase 1 (LIMK1), regulates <i>Drosophila melanogaster</i> forgetting in olfactory learning paradigm. Previously, we have shown that <i>limk1</i> suppression in the specific types of nervous cells differently affects fly courtship memory. Here, we used Gal4 &gt; UAS system to induce <i>limk1</i> overexpression in the same types of neurons. <i>limk1</i> activation in the mushroom body, glia, and <i>fruitless</i> neurons decreased learning index compared to the control strain or the strain with <i>limk1</i> knockdown. In cholinergic and dopaminergic/serotoninergic neurons, both overexpression and knockdown of <i>limk1</i> impaired <i>Drosophila</i> short-term memory. Thus, proper balance of the <i>limk1 </i>activity is crucial for normal cognitive activity of the fruit fly.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586831","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 the Gut Microbiome and Bacterial Amyloids in the Development of Synucleinopathies","authors":"Nina P. Trubitsina,&nbsp;Anton B. Matiiv,&nbsp;Tatyana M. Rogoza,&nbsp;Anna A. Zudilova,&nbsp;Mariya D. Bezgina,&nbsp;Galina A. Zhouravleva,&nbsp;Stanislav A. Bondarev","doi":"10.1134/S0006297924030118","DOIUrl":"10.1134/S0006297924030118","url":null,"abstract":"<p>Less than ten years ago, evidence began to accumulate about association between the changes in the composition of gut microbiota and development of human synucleinopathies, in particular sporadic form of Parkinson’s disease. We collected data from more than one hundred and thirty experimental studies that reported similar results and summarized the frequencies of detection of different groups of bacteria in these studies. It is important to note that it is extremely rare that a unidirectional change in the population of one or another group of microorganisms (only an elevation or only a reduction) was detected in the patients with Parkinson’s disease. However, we were able to identify several groups of bacteria that were overrepresented in the patients with Parkinson’s disease in the analyzed studies. There are various hypotheses about the molecular mechanisms that explain such relationships. Usually, α-synuclein aggregation is associated with the development of inflammatory processes that occur in response to the changes in the microbiome. However, experimental evidence is accumulating on the influence of bacterial proteins, including amyloids (curli), as well as various metabolites, on the α-synuclein aggregation. In the review, we provided up-to-date information about such examples.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586833","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":"Erratum to: Viral Vectors in Gene Replacement Therapy","authors":"Ekaterina Minskaia,&nbsp;Alima Galieva,&nbsp;Alexander D. Egorov,&nbsp;Roman Ivanov,&nbsp;Alexander Karabelsky","doi":"10.1134/S0006297924030167","DOIUrl":"10.1134/S0006297924030167","url":null,"abstract":"","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140580167","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":"Structure- and Cation-Dependent Mechanism of Interaction of Tricyclic Antidepressants with NMDA Receptor According to Molecular Modeling Data","authors":"Daria A. Belinskaia,&nbsp;Natalia N. Shestakova","doi":"10.1134/S0006297924030106","DOIUrl":"10.1134/S0006297924030106","url":null,"abstract":"<p>Some tricyclic antidepressants (TCAs), including amitriptyline (ATL), clomipramine (CLO), and desipramine (DES), are known to be effective for management of neuropathic pain. It was previously determined that ATL, CLO, and DES are capable of voltage-dependent blocking of NMDA receptors of glutamate (NMDAR), which play a key role in pathogenesis of neuropathic pain. Despite the similar structure of ATL, CLO, and DES, efficacy of their interaction with NMDAR varies significantly. In the study presented here, we applied molecular modeling methods to investigate the mechanism of binding of ATL, CLO, and DES to NMDAR and to identify structural features of the drugs that determine their inhibitory activity against NMDAR. Molecular docking of the studied TCAs into the NMDAR channel was performed. Conformational behavior of the obtained complexes in the lipid bilayer was simulated by the method of molecular dynamics (MD). A single binding site (upper) for the tertiary amines ATL and CLO and two binding sites (upper and lower) for the secondary amine DES were identified inside the NMDAR channel. The upper and lower binding sites are located along the channel axis at different distances from the extracellular side of the plasma membrane. MD simulation revealed that the position of DES in the lower site is stabilized only in the presence of sodium cation inside the NMDAR channel. DES binds more strongly to NMDAR compared to ATL and CLO due to simultaneous interaction of two hydrogen atoms of its cationic group with the asparagine residues of the ion pore of the receptor. This feature may be responsible for the stronger side effects of DES. It has been hypothesized that ATL binds to NMDAR less efficiently compared to DES and CLO due to its lower conformational mobility. The identified features of the structure- and cation-dependent mechanism of interaction between TCAs and NMDAR will help in the further development of effective and safe analgesic therapy.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586751","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 I182, R187, and K188 Amino Acid Residues in the Catalytic Domain of HIV-1 Integrase in the Processes of Reverse Transcription and Integration","authors":"Tatiana F. Kikhai,&nbsp;Yulia Yu. Agapkina,&nbsp;Tatiana A. Prikazchikova,&nbsp;Maria V. Vdovina,&nbsp;Sofia P. Shekhtman,&nbsp;Sofia V. Fomicheva,&nbsp;Sergey P. Korolev,&nbsp;Marina B. Gottikh","doi":"10.1134/S0006297924030076","DOIUrl":"10.1134/S0006297924030076","url":null,"abstract":"<p>Structural organization of HIV-1 integrase is based on a tetramer formed by two protein dimers. Within this tetramer, the catalytic domain of one subunit of the first dimer interacts with the N-terminal domain of the second dimer subunit. It is the tetrameric structure that allows both ends of the viral DNA to be correctly positioned relative to the cellular DNA and to realize catalytic functions of integrase, namely 3′-processing and strand transfer. However, during the HIV-1 replicative cycle, integrase is responsible not only for the integration stage, it is also involved in reverse transcription and is necessary at the stage of capsid formation of the newly formed virions. It has been suggested that HIV-1 integrase is a structurally dynamic protein and its biological functions depend on its structure. Accordingly, studying interactions between the domains of integrase that provide its tetrameric structure is important for understanding its multiple functions. In this work, we investigated the role of three amino acids of the catalytic domain, I182, R187, and K188, located in the contact region of two integrase dimers in the tetramer structure, in reverse transcription and integration. It has been shown that the R187 residue is extremely important for formation of the correct integrase structure, which is necessary at all stages of its functional activity. The I182 residue is necessary for successful integration and is not important for reverse transcription, while the K188 residue, on the contrary, is involved in formation of the integrase structure, which is important for the effective reverse transcription.</p>","PeriodicalId":483,"journal":{"name":"Biochemistry (Moscow)","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140586763","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}