Russian Journal of Bioorganic Chemistry最新文献

{"title":"Production and Structural-Functional Characterization of a Recombinant HIV-1 Env Trimer Based on the Consensus Sequence of the Most Prevalent Strains in the Russian Federation","authors":"I. A. Favorskaya,&nbsp;I. O. Ilyasov,&nbsp;I. A. Alekseeva,&nbsp;E. I. Ryabova,&nbsp;A. A. Antonova,&nbsp;D. A. Kleymenov,&nbsp;V. A. Gushchin,&nbsp;A. D. Burtseva,&nbsp;A. V. Moiseenko,&nbsp;T. S. Trifonova,&nbsp;V. O. Popov,&nbsp;N. N. Sluchanko,&nbsp;K. M. Boyko,&nbsp;D. V. Shcheblyakov,&nbsp;D. Yu. Logunov","doi":"10.1134/S1068162026601953","DOIUrl":"10.1134/S1068162026601953","url":null,"abstract":"<p><b>Objective:</b> The development of a vaccine candidate for specific active immunoprophylaxis against HIV-1 infection, based on the structure-guided design of HIV-1 Env proteins, is considered one of the most promising approaches to creating an immunogen capable of inducing broadly neutralizing antibodies (bnAbs). However, the high diversity of HIV-1 implies that immunogens based on a single specific strain may be ineffective against other circulating variants. Consequently, there is a need to develop an antigen capable of neutralizing a broad spectrum of HIV-1 genetic variants while accounting for regional strain characteristics. <b>Methods:</b> In this study, based on the sequences of Russian strains, a HIV-1 Env surface antigen and its variant with additional mutations—optimized for engagement with germline precursors of VRC01-class bnAbs—were developed and characterized. <b>Results and Discussion:</b> The CON-RUS SOSIP-v.9.3 antigen was designed based on a consensus amino acid sequence derived from the most prevalent HIV-1 variants in the Russian Federation (A6, B, CRF02_AG, and CRF63_02A6), with stabilizing SOSIP.v9.3 and TD8 mutations. The CON-RUS SOSIP-v.9.3_GT01 variant was further engineered with additional mutations to enhance binding affinity for the germline precursor of the VRC01 antibody. Biochemical characterization by BN-PAGE and SEC-MALS confirmed that both constructs predominantly form trimers with a molecular weight consistent with the expected size (~220 kDa excluding glycans). Negative-stain electron microscopy revealed that the majority of CON-RUS SOSIP-v.9.3 molecules adopt a closed conformation, as demonstrated by 2D class averaging and 3D reconstruction fitting to the closed-state BG505 SOSIP.664 structure (PDB ID: 3J5M). ELISA showed that mature VRC01 (mVRC01) binds both CON-RUS SOSIP-v.9.3 and CON-RUS SOSIP-v.9.3_GT01 with affinity comparable to reference BG505 SOSIP proteins. However, while no binding of CON-RUS SOSIP-v.9.3 to germline VRC01 (gVRC01) was detected, the GT01 modification enabled weak binding to gVRC01, although this was significantly lower than that of the BG505 SOSIP variant carrying analogous mutations. <b>Conclusions:</b> Based on the consensus sequence of HIV-1 strains prevalent in the Russian Federation, two recombinant Env constructs (CON-RUS SOSIP-v.9.3 and CON-RUS SOSIP-v.9.3_GT01) were developed, which predominantly adopt a trimeric organization and effectively engage the mature VRC01 antibody.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Green Synthesis to Biological Insight: A Multifaceted Study of Dibutyl (2-amino-3-cyano-4H-chromen-4-yl)phosphonates via DFT, ADMET, Docking, and In Vitro Assays","authors":"Sumithra Poreddy,&nbsp;Mohan Gundluru,&nbsp;Surendra Pothuraju,&nbsp;Santhisudha Sarva,&nbsp;Poojitha Bellala,&nbsp;Sunitha Gundubogula,&nbsp;Jyothibabu Sajila Arya,&nbsp;Suresh Reddy Cirandur","doi":"10.1134/S1068162025602952","DOIUrl":"10.1134/S1068162025602952","url":null,"abstract":"<p><b>Objective:</b> A green, solvent-free multicomponent synthesis of dibutyl (2-amino-3-cyano-4<i>H</i>-chromen-4-yl)phosphonates was developed using a homopiperazine catalyst under ultrasound irradiation to generate multifunctional scaffolds with therapeutic potential. <b>Methods:</b> Structural stability and electronic properties of the synthesized compounds were evaluated <i>via</i> Density Functional Theory (DFT). Molecular docking was performed against EGFR, HER2, MMP-9, TGFBR1, and VEGFR2, while ADMET modeling assessed pharmacokinetic profiles and toxicity risks. Biological evaluations included antioxidant, antimicrobial, and cytotoxicity assays. <b>Results and Discussion:</b> DFT calculations confirmed molecular stability and favorable reactivity descriptors. Molecular docking revealed potent multitarget binding affinity, particularly for compounds <b>4h</b>, <b>4g</b>, and <b>4b</b>. ADMET analysis indicated promising drug-like profiles with acceptable toxicity. <i>In vitro</i> assays demonstrated potent antioxidant activity, broad-spectrum antimicrobial effects, and significant cytotoxicity against MCF-7, MDA-MB-231, DU-145, HeLa, and HepG2 cell lines. Notably, compounds <b>4h</b>, <b>4g</b>, <b>4b</b>, <b>4l</b>, and <b>4k</b> exhibited superior cytotoxic efficacy compared to doxorubicin. Observed bioactivity correlated with electronic features, including MEP distribution and frontier molecular orbital energies. <b>Conclusions:</b> The integration of green synthesis, computational modeling, and biological validation highlights these chromenyl phosphonate hybrids as promising candidates for multitarget therapeutic applications, including oncology, oxidative stress modulation, and infectious diseases.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Studies of Bacteriorhodopsin: What Do We Know and What Did We Miss?","authors":"M. A. Dubinnyi,&nbsp;S. S. Bukhdruker,&nbsp;V. I. Borshchevskiy,&nbsp;M. V. Goncharuk,&nbsp;I. S. Okhrimenko,&nbsp;E. V. Bocharov,&nbsp;S. A. Goncharuk","doi":"10.1134/S1068162026601734","DOIUrl":"10.1134/S1068162026601734","url":null,"abstract":"<p>Bacteriorhodopsin is one of the most extensively studied membrane proteins. Since its discovery 55 years ago, thousands of papers have been published with the aim of elucidating its mechanism of action. Among these, structural biology studies are of particular importance, as they provide insight into the protein’s function at the most fundamental level. In this review, we summarize the key advances in the structural investigation of bacteriorhodopsin using the major high-resolution techniques: electron microscopy, atomic force microscopy, NMR spectroscopy, and X-ray crystallography. We also attempt to address the following questions: what data are still lacking for a complete understanding of this protein’s function, and how can each of these methods contribute to filling these gaps?</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Neurotoxins in the Study of the Spatial Structure of Nicotinic Acetylcholine Receptors—the Main Milestones","authors":"I. E. Kasheverov,&nbsp;Yu. N. Utkin,&nbsp;V. I. Tsetlin","doi":"10.1134/S1068162026601692","DOIUrl":"10.1134/S1068162026601692","url":null,"abstract":"<p>Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are among the most studied neurotransmitter receptors. They play an important role in nerve impulse transmission in the central and peripheral nervous systems and are also involved in regulating the functions of other systems, including the immune and cardiovascular ones. This review presents the main stages of elucidating the spatial structure of nAChRs, including a detailed characterization of their ligand-binding sites using natural and synthetic neurotoxins. These stages cover, in particular, the localization of binding sites on the receptor using modified ligands, crystallographic studies of various structural homologs of the receptor, including complexes with toxins, as well as recent cryoelectron microscopy data.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZHER2 Affibodies: A Versatile Platform for Diagnostics and Therapy of HER2Overexpressing Cancers","authors":"I. I. Tyuryaeva,&nbsp;E. I. Trosko,&nbsp;D. A. Luzik","doi":"10.1134/S1068162026601862","DOIUrl":"10.1134/S1068162026601862","url":null,"abstract":"<p>Overexpression of the human epidermal growth factor receptor 2 (HER2) is a well-established diagnostic and prognostic biomarker in certain malignancies and is generally associated with aggressive metastatic progression and poor clinical outcome. HER2-directed diagnostic and therapeutic strategies have achieved substantial clinical success, with monoclonal antibodies remaining the current gold standard. Nevertheless, this approach is limited by several important factors, including complex and expensive manufacturing processes and the relatively low stability of antibodies. These limitations underscore the need for alternative targeting agents. Among the most promising alternatives are affibodies, a class of small engineered proteins derived from the Z domain of staphylococcal protein A. In particular, the ZHER2 affibody family constitutes a promising group of small proteins that exhibit high affinity for the target receptor and have demonstrated success in realworld clinical applications of diagnostics and therapy of HER2overexpressing tumors. In this report, we summarize the development and optimization history of these affibodies, their structural features, advantages and limitations for clinical applications. In addition, we present our own original data highlighting the utility of ZHER2 affibodies for <i>in vitro</i> diagnostics of malignant tumors.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Biology of Zinc-Binding Proteins and Peptides","authors":"U. V. Bulgakova,&nbsp;K. I. Balagurov,&nbsp;A. Yu. Rudenko,&nbsp;K. N. Aysin,&nbsp;S. A. Goncharuk,&nbsp;S. S. Mariasina,&nbsp;P. G. Georgiev,&nbsp;E. V. Bocharov,&nbsp;V. I. Polshakov","doi":"10.1134/S1068162026601655","DOIUrl":"10.1134/S1068162026601655","url":null,"abstract":"<p>This review systematizes current data on the structural organization, coordination chemistry, and functional roles of zinc-binding proteins and peptides. The mechanisms by which Zn²⁺ ions participate in homeostasis, enzymatic catalysis, signal transduction, and pathological processes are analyzed. A large dataset of zinc-containing protein structures deposited in the Protein Data Bank was examined. Tetrahedral coordination geometry predominates for zinc ions (over 67% of structures), with more than 92% of coordinating groups represented by residues of Cys, His, Asp, Glu, and water molecules. The most common coordination motifs are Cys₄, Cys₃His, and Cys₂His₂. Zinc ions perform both structural roles (e.g., zinc fingers, metallothioneins) and catalytic functions (including water activation and substrate polarization). The mechanisms of Zn²⁺-dependent enzymes are discussed, including carbonic anhydrases, carboxypeptidase A, superoxide dismutases, alcohol dehydrogenases, alkaline phosphatases, and matrix metalloproteinases. Zinc homeostasis systems (ZIP importers, ZnT exporters, and metallothioneins) and their regulation by transcription factors MTF-1 (in vertebrates) and ZntR (in bacteria) are described. Evidence is reviewed for the modulation of a wide range of membrane receptors by Zn²⁺ ions through multiple mechanisms, including allosteric inhibition or potentiation, stabilization of protein–protein interactions (“zinc clasps”), and ligand binding. A structural classification of zinc fingers is presented, ranging from classical CysHis₂ domains to more complex architectures containing two Zn²⁺ ions. Using the β-amyloid peptide (Aβ) as an example, the role of Zn²⁺ in pathogenic oligomerization is demonstrated, and approaches to inhibit this process are outlined. The conservation of ligand environments combined with variability in zinc coordination numbers provides a balance between rigidity and lability, enabling both structural and catalytic functions. Disruption of zinc homeostasis underlies a range of pathologies, including neurodegenerative diseases, diabetes, immune deficiency, and cancer. This review summarizes key concepts essential for further studies of Zn²⁺ ions in biological systems and for the development of therapeutic strategies based on controlling zinc-dependent biological processes.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lawsone-Derived Heterocycles: Synthetic Strategies, Structure–Activity Relationships, and Therapeutic Applications","authors":"J. P. Sonawane,&nbsp;V. S. Patil,&nbsp;V. K. Suryawanshi,&nbsp;S. S. Nandre,&nbsp;P. M. Raotale,&nbsp;S. R. Patil","doi":"10.1134/S1068162025602836","DOIUrl":"10.1134/S1068162025602836","url":null,"abstract":"<p>Lawsone (2-hydroxy-1,4-naphthoquinone) has emerged as a privileged scaffold for the construction of bioactive heterocycles with applications spanning antimicrobial, antioxidant, antimalarial, anticancer, and antiplatelet therapies. This review distills advances in both classical (nucleophilic addition, cyclization) and modern (C–H activation, multicomponent, photoinduced) synthetic routes under green chemistry protocols, as well as functionalization strategies that modulate biological activity. Structure–activity relationship studies indicate that strategically incorporating lipophilic chains, aromatic groups, and heterocyclic rings improves target binding and enhances cellular potency. The growing portfolio of lawsone–metal complexes further extends therapeutic potential through dual antimicrobial and anticancer mechanisms. Despite these promising findings, comprehensive <i>in vivo</i> validation, metabolic stability, and toxicity assessments remain scarce. Future efforts should prioritize detailed SAR studies, advanced delivery platforms, and combinatorial regimens to accelerate the clinical translation of lawsone-derived drug candidates.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NMR as a Video-(Game): Constructing Super-Resolution Cross-Peak Trajectories in Protein Spectroscopy","authors":"Chng Jing Hang,&nbsp;Yevheniia Kuznietsova,&nbsp;Mikhail Fillipov,&nbsp;Konstantin Pervushin","doi":"10.1134/S1068162026601771","DOIUrl":"10.1134/S1068162026601771","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Objective:&lt;/b&gt; High-resolution multidimensional NMR spectroscopy of proteins remains limited by long acquisition times, sensitivity constraints, and severe peak overlap, particularly for larger systems. Conventional 3D and higher-dimensional experiments trade experimental efficiency for resolution, while post-acquisition analysis often becomes the dominant bottleneck. &lt;b&gt;Methods:&lt;/b&gt; Here, we present a new framework that redefines both how NMR experiments are constructed and how they are executed and analyzed, by treating an AI agent-controllable series of 2D spectra as a spatiotemporal dataset analogous to a video. Our approach is based on temperature-dependent series of reduced-dimensionality 2D HSQC and novel RDL-TROSY experiments, in which each 2D [&lt;sup&gt;1&lt;/sup&gt;H,&lt;sup&gt;15&lt;/sup&gt;N] cross-peak is controllably shifted and split in proportion to the &lt;sup&gt;13&lt;/sup&gt;C chemical shift of the J-coupled carbons. We propose treating a variable-temperature (VT) series as a pseudo-temporal video sequence in which each cross-peak traces a physically motivated trajectory through frequency space. The proportionality coefficient (α) of this reduced-dimensionality encoding is systematically and programmatically varied together with the temperature providing full control for constructing optimal cross-peak trajectories. As a result, individual resonances follow predictable, spectral acquisition time-controllable trajectories in the 2D spectral plane across the series, which can be executed by an autonomous AI agent directly interacting with the NMR GUI layer. Each spectrum represents a single “frame,” while temperature and RD controls serve as the temporal dimension. We describe two complementary super-resolution strategies: a cross-peak model-independent approach based on deep-learning video super-resolution that leverages temporal redundancy to sharpen per-frame peak shapes, and a model-based approach that derives the exact mathematical form of the peak trajectories and uses it to design acquisition schedules that render individual peak paths maximally distinct and amenable for algorithmic deconvolution. &lt;b&gt;Results and Discussion:&lt;/b&gt; As a result, we obtained full backbone resonance assignment in the wide temperature range (279–318 K) with one degree Kelvin resolution in a test protein in an automatic manner in the time frame typically required for collection of a single 3D NMR dataset. &lt;b&gt;Conclusions:&lt;/b&gt; The VT-NMR experiment is reconceptualised as a video processing problem, with the temperature axis acting as a pseudo-temporal dimension that enables inter-frame pooling to resolve peaks not resolved in any single spectrum. The RD-HSQC provides simultaneous spectral, temporal, and topological discrimination. The agnostic super-resolution strategy improves per-frame quality without physical assumptions, while the model-based strategy uses spectral-width modulation to convert &lt;sup&gt;13&lt;/sup&gt;C&lt;sub&gt;α&lt;/sub&gt; diversity into engineered inter-trajectory separation. A","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Point Substitution N33D in the Light Chain of Neutralizing Antibody REGN10987 Increases the Fab Affinity to RBD of Omicron BA.1 SARS-CoV-2 Variant. In Silico Study","authors":"D. E. Nolde,&nbsp;M. V. Kocharovskaya,&nbsp;A. V. Popov,&nbsp;M. P. Kirpichnikov,&nbsp;E. N. Lyukmanova,&nbsp;Z. O. Shenkarev","doi":"10.1134/S1068162026600662","DOIUrl":"10.1134/S1068162026600662","url":null,"abstract":"<p><b>Objective:</b> One of the effective approaches for the treatment of viral diseases is to use neutralizing antibodies. REGN10987 antibody (imdevimab) binds to the receptor-binding domain (RBD) of the SARS-CoV-2 <i>S</i>-protein, preventing the virus from binding to its receptor, angiotensin-converting enzyme 2, thereby blocking entry into cells. Although REGN10987 is effective against the Wuhan, Alpha, and Delta variants of the virus, it has lost potency against the Omicron BA.1 (B.1.1.529) and subsequent variants. This evasion is partially caused by the N440K mutation of the RBD, which is located at the interface with the light chain of REGN10987. We propose a variant of REGN10987 containing the N33D point mutation in the light chain, which should enhance interaction with the Omicron RBD by establishing an additional K440–D33 salt bridge. <b>Methods:</b> Structure and stability of complexes formed by the Wuhan and Omicron BA.1 RBD variants with REGN10987-Fab[N33D] were investigated using molecular dynamics (MD) and dissociation free energy (Δ<i>G</i>) calculations for the RBD/Fab complexes, by umbrella sampling and potential of mean force analysis (US-PMF). <b>Results and Discussion:</b> Significant variations in the structure of RBD/Fab complexes during MD resulted in a wide range of calculated Δ<i>G</i> values. Nevertheless, the results suggest that the N33D substitution increases REGN10987-Fab affinity for the Omicron BA.1 RBD and complex’s stability, while preserving its affinity for the Wuhan RBD. <b>Conclusions:</b> The results suggest that computer-aided design could be used to create neutralizing antibodies to treat existing and emerging virus strains. However, new fast and reliable computational approaches are needed to quantitatively assess biomolecule affinity.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural Studies of the Eukaryotic Translation Initiation Factor eIF5A from Candida albicans by High-Resolution NMR Spectroscopy and X-Ray Crystallography","authors":"V. E. Gonyalin,&nbsp;P. V. Egorova,&nbsp;E. E. K. Agboigba,&nbsp;Sh. Z. Validov,&nbsp;A. D. Biktimirov,&nbsp;N. S. Garaeva,&nbsp;K. M. Boyko,&nbsp;V. V. Klochkov,&nbsp;A. V. Aganov,&nbsp;M. M. Yusupov,&nbsp;K. S. Usachev","doi":"10.1134/S1068162026601746","DOIUrl":"10.1134/S1068162026601746","url":null,"abstract":"<p><b>Objective:</b> Eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein involved in translation elongation during the synthesis of polyproline motif and require hypusine modification for its activity. Structural differences in eIF5A form eukaryotic pathogens could aid antimicrobial development. This study presents structural data on <i>Candida albicans</i> eIF5A obtained by NMR and X-ray crystallography. <b>Methods:</b> Protein cloning, expression and purification were used for obtaining sample for structural studies and NMR spectroscopy and X-ray crystallography experiments were performed. <b>Results and Discussion:</b> In this work, for the first time, the three-dimensional structure of the eIF5A protein from the pathogenic yeast-like fungus <i>Candida albicans</i> was determined by X-ray crystallography at a resolution of 2.6 Å, and a comparative analysis of the structural data with homologous proteins from <i>S. cerevisiae</i> and <i>H. sapiens</i> was performed. A high degree of conservation in the spatial organization of eIF5A was demonstrated: the mutual arrangement of domains and secondary structure elements is consistent with homologous proteins from other organisms. The obtained structural data are consistent with NMR spectroscopy data and complement the understanding of the spatial organization of proteins of this class. <b>Conclusions:</b> The presented structure of the protein from <i>Candida albicans</i> can serve as a basis for further fundamental studies of its function, as well as for the development of inhibitors targeting enzymes of the hypusination system as a potential target for antifungal therapy.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"52 3","pages":""},"PeriodicalIF":1.7,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147829444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}