Article
Multidisciplinary Sciences
Xiaofeng Chu, Xin Su, Mingdong Liu, Li Li, Tianhao Li, Yicheng Qin, Guoliang Lu, Lei Qi, Yunhui Liu, Jinzhong Lin, Qing-Tao Shen
Summary: This study investigates the effect of annealing on biological macromolecules using the 70S ribosome as a model. Experimental results show that annealing with a fast cooling rate can enhance the homogeneity and resolution of the ribosome, reaching a minimum energy state in the free-energy landscape. This approach has potential applications in improving protein stability and synchronizing proteins on a single-molecule level.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Yuhei Chadani, Nobuyuki Sugata, Tatsuya Niwa, Yosuke Ito, Shintaro Iwasaki, Hideki Taguchi
Summary: Translation elongation is essential for organisms to produce their proteomes, but there is a risk of elongation abortion due to sequences like intrinsic ribosome destabilization (IRD) sequences. Most potential IRD sequences in the middle of open reading frames remain hidden and do not interrupt translation, as the nascent polypeptide itself acts as a bridge in the ribosome, protecting it from dissociation. This inherent ability of nascent polypeptide products ensures elongation continuity.
Article
Multidisciplinary Sciences
Chetana Baliga, Tyler J. Brown, Tanja Florin, Sarah Colon, Vallari Shah, Kornelia J. Skowron, Amira Kefi, Teresa Szal, Dorota Klepacki, Terry W. Moore, Nora Vazquez-Laslop, Alexander S. Mankin
Summary: Apidaecin is an 18-amino-acid proline-rich antibacterial peptide produced by bees that inhibits translation termination by invading the ribosome's nascent peptide exit tunnel. By analyzing the activity of different mutants with single-amino-acid substitutions, researchers were able to map critical interactions with the ribosome, tRNA, and release factors, as well as identify a segment of Api that tolerates amino acid substitutions for potential pharmacological improvement.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Infectious Diseases
Tobias Ludwig, Andor Krizsan, Gubran Khalil Mohammed, Ralf Hoffmann
Summary: Given the global spread of drug-resistant bacteria and the emergence of pan-resistant bacteria, there is an urgent need for antimicrobials with new mechanisms of action. Antimicrobial peptides (AMPs), including proline-rich AMPs (PrAMPs), are a promising class. In this study, a designer peptide called Api805 was created by combining the N- and C-terminal sequences of PrAMPs Api137 and drosocin. Api805 exhibited similar activity against two Escherichia coli B strains, but was inactive against E. coli K12 strain BW25113. The differences in activity could not be explained by the measured dissociation constants for 70S ribosome preparations from the different strains.
Article
Biochemistry & Molecular Biology
Alena Paleskava, Elena M. Maksimova, Daria S. Vinogradova, Pavel S. Kasatsky, Stanislav Kirillov, Andrey L. Konevega
Summary: The study found that replacing elongation factors with thermophilic proteins in an in vitro translation system affected the rates of A-site binding and decoding reactions, while translocation kinetics were influenced differently. This suggests the importance of elongation factors in the translation process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Daniel J. Bennison, Jose A. Nakamoto, Timothy D. Craggs, Pohl Milon, John B. Rafferty, Rebecca M. Corrigan
Summary: During nutrient limitation, bacteria produce (p)ppGpp as effectors of the stringent response. This molecule inhibits the activity of ribosome-associated GTPases, affecting ribosome assembly and bacterial growth, highlighting a major mechanism of stringent response control.
Article
Multidisciplinary Sciences
Maximiliane Wieland, Mikael Holm, Emily J. Rundlet, Martino Morici, Timm O. Koller, Tinashe P. Maviza, Domen Pogorevc, Ilya A. Osterman, Rolf Muller, Scott C. Blanchard, Daniel N. Wilson
Summary: In this study, the inhibition mechanism of ArgB on EF-G was investigated using cryo-EM and smFRET techniques. It was found that ArgB inhibits intermediate steps of the translocation mechanism by binding specifically to EF-G on the ribosome without interfering with ribosome binding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Yun-Ting Tseng, Yu-Cheng Sung, Ching-Yu Liu, Kai-Yin Lo
Summary: This study shows that eIF4G1 is directly involved in the biogenesis of the 60S ribosomal subunit in Saccharomyces cerevisiae cells. It plays a crucial role in facilitating PET maturation and 27S processing.
JOURNAL OF CELL SCIENCE
(2022)
Article
Microbiology
Laura Fernandez-Garcia, Maria Tomas, Thomas K. Wood
Summary: By studying E. coli proteins, we found that the GTPase RsgA can inhibit lytic phage T4 by inactivating ribosomes.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra Brakel, Andor Krizsan, Renke Itzenga, Carl N. Kraus, Laszlo Otvos, Ralf Hoffmann
Summary: Proline-rich antimicrobial peptide ARV-1502 and its analogs exhibit strong antimicrobial effects against Enterobacteriaceae bacteria. The study reveals that these analogs exert antimicrobial activity by binding to the bacterial 70S ribosome, and the binding site overlaps with other antimicrobial peptides and antibiotics. Substitutions in the ribosomal binding motif affect binding and inhibitory activity, and substitutions with higher hydrophobicity or positive net charge improve ribosome binding, translation inhibition, and bacterial uptake.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Leonid Anikin, Dimitri G. Pestov
Summary: Aminoacridines, historically used as antiseptic and antiparasitic agents, could be repurposed for therapeutic use and new drug development. In this study, the effects of 9-aminoacridine on pre-rRNA metabolism in mammalian cells were investigated. The results showed that 9-aminoacridine inhibits both pre-rRNA transcription and processing, leading to the disruption of ribosome biogenesis. The ability of 9-aminoacridine to bind to RNA in vitro suggests its potential as a new ribosome biogenesis inhibitor.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Zhiyong Liu, Yanan Pang, Yin Jia, Qin Qin, Rui Wang, Wei Li, Jie Jing, Haidong Liu, Shanrong Liu
Summary: This study found that SNORA23 regulates ribosome biogenesis in hepatocellular carcinoma (HCC) by impairing the 2'-O-ribose methylation of 28S rRNA. SNORA23 inhibits the proliferation, migration, and invasion of HCC cells in vitro and in vivo. It is regulated by the PI3K/Akt/mTOR signaling pathway and inhibits the phosphorylation of 4E binding protein 1.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ivan B. Lomakin, Swapnil C. Devarkar, Shivali Patel, Ayman Grada, Christopher G. Bunick
Summary: Acne vulgaris is a chronic skin disease that negatively affects the physical and mental health of approximately 1 billion people worldwide. Through cryogenic electron microscopy, we discovered that sarecycline, an antibiotic against Cutibacterium acnes, can inhibit two active sites on the ribosome of this bacterium, unlike the previously detected one site on a model ribosome. The structure also revealed unique features of the ribosomal RNA and proteins in Cutibacterium acnes.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Alix A. J. Rouault, Paul Buscaglia, Julien A. Sebag
Summary: The melanocortin receptor accessory protein 2 (MRAP2) plays a crucial role in modulating the signaling pathway of the ghrelin receptor growth hormone secretagogue receptor 1a (GHSR1a), affecting appetite and insulin secretion. By altering the phosphorylation state of GHSR1a and inhibiting the interaction of GRK2 and PKC with the receptor, MRAP2 modifies GHSR1a signaling and diminishes the recruitment of fl-arrestin.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Oncology
Stefania Zuppone, Chiara Assalini, Claudia Minici, Oronza A. Botrugno, Flavio Curnis, Massimo Degano, Angelo Corti, Francesco Montorsi, Andrea Salonia, Riccardo Vago
Summary: In this study, a genetically modified protein called RGD-SAP was developed by modifying the structure of a plant-derived ribosome inactivating protein. The study demonstrated the anti-tumor activity of RGD-SAP in bladder cancer and its potential for clinical application.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vera A. Alferova, Tinashe P. Maviza, Mikhail V. Biryukov, Yuliya V. Zakalyukina, Vladimir I. Polshakov, Petr V. Sergiev, Vladimir A. Korshun, Ilya A. Osterman
Summary: Recently discovered aromatic polyketide tetracenomycins are potent inhibitors of protein synthesis, with a unique binding site located within the tunnel of the large ribosomal subunit. We report the isolation and structure elucidation of a novel tetracenomycin congener, O4-Me-tetracenomycin C, which is isomeric to tetracenomycin X. However, unlike tetracenomycin X, O4-Me-tetracenomycin C showed no antimicrobial activity and failed to inhibit protein synthesis in vitro. Structural alignment of tetracenomycins revealed the crucial role of the 4-hydroxyl group. These findings are important for the development of semi-synthetic tetracenomycins as potential antibacterials.
Article
Biochemistry & Molecular Biology
Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Olga O. Grigoryeva, Mikhail Gulyaev, Olga S. Pavlova, Sofia S. Mariasina, Olga Yu Frolova, Marina Kurkina, Galina Baydakova, Ekaterina Yu Zakharova, Maria Marey, Dmitry A. Tsarev, Vadim N. Tashlitsky, Vladimir S. Popov, Maxim L. Lovat, Vladimir I. Polshakov, Mikhail Yu Vyssokikh, Petr Sergiev
Summary: Mitoregulin (Mtln) is a mitochondrial peptide that enhances the function of respiratory complex I by modulating lipid composition. Knockout mice deficient in Mtln gene showed obesity on a high fat diet, which was attributed to enhanced fat accumulation based on magnetic resonance imaging. In addition, these mice exhibited elevated serum triglycerides, exhaustion of tricarboxylic acids cycle intermediates, and suboptimal oxidation of respiration substrates by mitochondria lacking Mtln.
Article
Biochemistry & Molecular Biology
George A. Saratov, Vasiliy I. Vladimirov, Alexey L. Novoselov, Rustam H. Ziganshin, Guo Chen, Timur N. Baymukhametov, Andrey L. Konevega, Alexey A. Belogurov, Anna A. Kudriaeva
Summary: In this study, the researchers characterized human constitutive and immune 20S and 26S/30S proteasomes using engineered versions fused with different subunits. They found that immunoproteasomes produced peptides that can be directly loaded onto HLA class I molecules, based on their hydrolysis of the multiple sclerosis autoantigen MBP. They identified five immunodominant core regions of MBP, and found that all peptides, except one, were associated with HLA I alleles known to increase MS risk. They also observed that certain HLA-A*44 molecules showed high affinity binding to a specific MBP peptide, potentially linking their protective phenotype to the depletion of autoreactive cytotoxic T cells or induction of CD8+ regulatory T cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Madhura N. Paranjpe, Valeria Marina, Aleksandr A. Grachev, Tinashe P. Maviza, Olga A. Tolicheva, Alena Paleskava, Ilya A. Osterman, Petr Sergiev, Andrey L. Konevega, Yury S. Polikanov, Matthieu G. Gagnon
Summary: Thermorubin (THR) is an antibiotic that can inhibit translation initiation and disrupt tRNA accommodation in the ribosomal A site, causing ribosome stalling at internal and termination codons. Our findings reveal that THR affects multiple steps of translation elongation and can coexist with P- and A-site tRNAs, allowing ribosomes to continue elongation in the presence of the drug.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tatiana Shtam, Vladimir Burdakov, Alina Garina, Luiza Garaeva, Nhan Hau Tran, Andrey Volnitskiy, Eva Kuus, Dmitry Amerkanov, Fedor Pack, Georgy Andreev, Andrey Lubinskiy, Konstantin Shabalin, Nicolay Verlov, Evgeniy Ivanov, Victor Ezhov, Dmitry Lebedev, Andrey L. Konevega
Summary: Proton boron capture therapy (PBCT) aims to enhance the biological effectiveness of proton therapy. However, experiments showed that the sensitizing potential of sodium borocaptate (BSH) did not significantly enhance the effect of proton radiation on glioma cells in vitro. The study also found that the previous increase in biological efficiency of proton irradiation in the presence of sodium borocaptate was not observed in prostate cancer cells.
SCIENTIFIC REPORTS
(2023)
Article
Infectious Diseases
Julia A. Pavlova, Andrey G. Tereshchenkov, Pavel A. Nazarov, Dmitrii A. Lukianov, Dmitry A. Skvortsov, Vladimir I. Polshakov, Byasilya F. Vasilieva, Olga V. Efremenkova, Mikhail Y. Kaiumov, Alena Paleskava, Andrey L. Konevega, Olga A. Dontsova, Ilya A. Osterman, Alexey A. Bogdanov, Natalia V. Sumbatyan
Summary: To improve the properties of antimicrobial compounds, new conjugates were synthesized and studied, which consisted of two different biologically active agents in a single chimeric molecule based on chloramphenicol and a hydrophobic cation. These conjugates, named CAM-Cn-BER, effectively bound to the bacterial ribosome and inhibited protein synthesis, similar to chloramphenicol. CAM-C8-BER displayed selective inhibition of Gram-positive bacteria and acted on both the ribosome and the cell membrane. Moreover, CAM-Cn-BERs did not inhibit eukaryotic translation and were non-toxic to eukaryotic cells.
Correction
Microbiology
Yuliya V. Zakalyukina, Ilya A. Osterman, Jacqueline Wolf, Meina Neumann-Schaal, Imen Nouioui, Mikhail V. Biryukov
ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Evgeniia A. Diatlova, Grigory V. Mechetin, Anna V. Yudkina, Vasily D. Zharkov, Natalia A. Torgasheva, Anton V. Endutkin, Olga V. Shulenina, Andrey L. Konevega, Irina P. Gileva, Sergei N. Shchelkunov, Dmitry O. Zharkov
Summary: The protein encoded by the D4R gene in vaccinia virus has both base excision repair uracil-DNA N-glycosylase (vvUNG) activity and acts as a processivity factor in the viral replication complex. The processivity of vvUNG has been characterized using the correlated cleavage assay, which suggests that it plays a role in lesion search through one-dimensional diffusion. Inhibitors carrying a tetrahydro-2,4,6-trioxopyrimidinylidene moiety can suppress the processivity of vvUNG.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Olga A. Averina, Oleg A. Permyakov, Mariia A. Emelianova, Olga O. Grigoryeva, Maxim L. Lovat, Anna E. Egorova, Andrei V. Grinchenko, Vadim V. Kumeiko, Maria V. Marey, Vasily N. Manskikh, Olga A. Dontsova, Mikhail Yu. Vysokikh, Petr V. Sergiev
Summary: Small peptides are important components of mitochondrial proteome, and the mitochondrial peptide Mtln plays a crucial role in respiratory complex I functioning and other processes in mitochondria. Knockout of Mtln in mice leads to obesity, triglyceride accumulation, and depletion of tricarboxylic acids cycle intermediates, indicating its important physiological functions. In addition, Mtln deficiency also impairs muscle strength, disrupts mitochondrial cardiolipin balance, and affects respiratory chain performance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Dmitrii Y. Y. Travin, Romain Jouan, Armelle Vigouroux, Satomi Inaba-Inoue, Joy Lachat, Fazal Haq, Tatiana Timchenko, Dmitry Sutormin, Svetlana Dubiley, Konstantinos Beis, Solange Morera, Konstantin Severinov, Peter Mergaert
Summary: The peptide antibiotic Phazolicin (PHZ) exhibits low resistance in Sinorhizobium meliloti due to its dual-entry mode through two different peptide transporters. This finding makes PHZ an attractive option for the development of biocontrol agents in agriculture.
Article
Pharmacology & Pharmacy
Kseniya Shapovalova, Georgy Zatonsky, Natalia Grammatikova, Ilya Osterman, Elizaveta Razumova, Andrey Shchekotikhin, Anna Tevyashova
Summary: Aminoglycosides, one of the earliest antibiotics used clinically, still hold promise for the development of new antibacterial agents. We synthesized 6''-deoxykanamycin A analogues and found that introducing guanidine residues improved their activity against S. aureus. Furthermore, these modified kanamycin A derivatives showed reduced susceptibility to resistance mechanisms associated with mutations of elongation factor G.
Article
Biochemistry & Molecular Biology
Nhan Hau Tran, Vyacheslav Ryzhov, Andrey Volnitskiy, Dmitry Amerkanov, Fedor Pack, Aleksander M. Golubev, Alexandr Arutyunyan, Anastasiia Spitsyna, Vladimir Burdakov, Dmitry Lebedev, Andrey L. Konevega, Tatiana Shtam, Yaroslav Marchenko
Summary: In this study, the potential of iron oxide nanoparticles as radiosensitizers in glioblastoma cells was evaluated. The results showed that the nanoparticles can significantly enhance the effect of X-ray irradiation, while having a weaker or no effect on gamma and proton irradiation. The findings suggest that the nanoparticles may enhance radiation therapy by generating secondary electrons.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Shao-Wei Liu, Xiao-Xu Zhai, Di Liu, Yu-Yu Liu, Li-Ying Sui, Ke-Ke Luo, Qin Yang, Fei-Na Li, Arina A. Nikandrova, Arina N. Imamutdinova, Dmitrii A. Lukianov, Ilya A. Osterman, Petr V. Sergiev, Ben-Yin Zhang, De-Jun Zhang, Chun-Mei Xue, Cheng-Hang Sun
Summary: This study investigates the biodiversity and bioactive secondary metabolites of cultivable actinobacteria isolated from the sediments of saline lakes on the Northern Tibetan Plateau. Through the use of metabolomics and genomics approaches, potential bioactive compounds were rapidly identified, including potential novel anthracycline compounds.
Article
Food Science & Technology
Tamara S. Novik, Elena I. Koveshnikova, Anatoly A. Kotlobay, Lyudmila P. Sycheva, Karine G. Kurochkina, Olga A. Averina, Maria V. Belopolskaya, Petr V. Sergiev, Olga A. Dontsova, Vassili N. Lazarev, Igor V. Maev, Margarita G. Kostyaeva, Artem V. Eremeev, Svetlana I. Chukina, Maria A. Lagarkova
Summary: This article presents the results of a comprehensive toxicity assessment of yeast-produced recombinant sweet-tasting proteins, brazzein and monellin. The study confirms the safety and non-toxicity of these proteins for mammalian organisms, opening up vast opportunities for their application as sugar alternatives in the food industry.
Review
Biochemistry & Molecular Biology
J. A. Buyuklyan, Yu. V. Zakalyukina, I. A. Osterman, M. V. Biryukov
Summary: Representatives of the phylum Actinomycetota are important sources of secondary metabolites, including antibiotics. However, the production of these metabolites in laboratory conditions is low and there is a continuous rediscovery of known antibiotics, making new molecules harder to find. Established approaches to increase antibiotic production have limitations and are not always successful. Genetic engineering technologies, such as mutagenesis-based genome editing, offer a more efficient way to control and increase the production of target metabolites.