Biochemistry Biochemistry最新文献

{"title":"Role of the Palmitoyl Group and of the Amphipathic α Helix in the Membrane Binding of the C-Terminus of G-Protein Receptor Kinase 4α/β","authors":"Marc-Antoine Millette,&nbsp;Ana Coutinho,&nbsp;Manuel Prieto and Christian Salesse*,&nbsp;","doi":"10.1021/acs.biochem.4c0049210.1021/acs.biochem.4c00492","DOIUrl":"https://doi.org/10.1021/acs.biochem.4c00492https://doi.org/10.1021/acs.biochem.4c00492","url":null,"abstract":"<p >Membrane binding of monotopic proteins can involve various post-translational modifications or a combination of some membrane-binding elements. For example, amphipathic α helices and palmitoylation could drive the membrane attachment of proteins. G-protein-coupled receptor kinases (GRKs) regulate the activity of G-protein-coupled receptors. Several members of the family of GRKs are acylated. Moreover, the C-terminus of GRK6 contains an amphipathic α helix and a palmitoyl group, which could also be the case for GRK4 isoforms. In our experiments, GRK4α/β-derived peptides of differing C-terminal lengths (Cter-GRK4α/β variants) were thus studied to discriminate the individual role of the palmitoyl group and amphipathic α helix of Cter-GRK4α/β in its membrane binding. The membrane binding of the Cter-GRK4α/β variants was studied by comparing their maximum insertion pressure (MIP) to lipid monolayers as well as their intrinsic fluorescence properties using large unilamellar vesicles. The MIP data show a higher level of binding of the palmitoylated longest GRK4α/β variant. Moreover, MIP measurements in the absence and presence of 15 mol % of the negatively charged phosphoserine demonstrated that the amphipathic α helix of Cter-GRK4α/β plays a major role in its membrane binding. Accordingly, partition studies of the Cter-GRK4α/β variants to membranes by fluorescence spectroscopy demonstrate the involvement of the palmitoyl group and the amphipathic α helix of the C-terminus of GRK4α/β in its membrane binding. Altogether, the data show that both the palmitoyl group and the amphipathic helix highly favor membrane binding of the C-terminus of GRK4α/β, which should facilitate the proper anchoring of GRK4α/β and phosphorylation of GPCRs.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"64 5","pages":"987–1005 987–1005"},"PeriodicalIF":2.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sortase-Mediated Fluorescent Labeling of eIF4E for Investigating Translation Initiation Mechanisms","authors":"Justin Pi,&nbsp; and ,&nbsp;Simpson Joseph*,&nbsp;","doi":"10.1021/acs.biochem.4c0085110.1021/acs.biochem.4c00851","DOIUrl":"https://doi.org/10.1021/acs.biochem.4c00851https://doi.org/10.1021/acs.biochem.4c00851","url":null,"abstract":"<p >Translation initiation represents a critical regulatory step in gene expression, orchestrated by the interaction of eukaryotic initiation factor 4E (eIF4E) with the 7-methylguanosine (m⁷G) cap structure at the 5′ end of mRNA. This interaction enables eIF4F, composed of eIF4E, eIF4G, and eIF4A, to recruit the 43S preinitiation complex to the mRNA 5′ end. The activity of eIF4E is tightly regulated and often dysregulated in cancer, neurological disorders, and viral infections. To investigate the interactions of human eIF4E with m⁷G-RNA and eIF4G, we engineered single-cysteine mutants of eIF4E to enable fluorescent dye attachment. However, these mutants presented challenges in purification and exhibited diminished activity. To overcome these issues, we developed a method to fluorescently label eIF4E via sortase-mediated transpeptidation. Our results demonstrate that sortase-labeled eIF4E retains activity comparable to wild-type eIF4E. This approach provides a valuable tool for studying the dynamic mechanisms of translation initiation and its regulation.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":"64 5","pages":"1099–1108 1099–1108"},"PeriodicalIF":2.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143533938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Cooperation of the Two Pore-Forming Transmembrane Motifs Regulates the β-Barrel Pore Formation by Listeriolysin O.","authors":"Kusum Lata, Koyel Nandy, Geetika, Kausik Chattopadhyay","doi":"10.1021/acs.biochem.4c00592","DOIUrl":"10.1021/acs.biochem.4c00592","url":null,"abstract":"<p><p>Listeriolysin O (LLO) is a potent membrane-damaging pore-forming toxin (PFT) secreted by the bacterial pathogen <i>Listeria monocytogenes</i>. LLO belongs to the family of cholesterol-dependent cytolysins (CDCs), which specifically target cholesterol-containing cell membranes to form oligomeric pores and induce membrane damage. CDCs, including LLO, harbor designated pore-forming motifs. In the soluble monomeric state, these motifs are present as helical segments (two transmembrane helices (TMHs); TMH1 and TMH2), and in the course of oligomeric pore formation, they convert into transmembrane β-hairpins to form the β-barrel scaffold of the CDC pores. Despite their well-established role in forming the β-barrel pore scaffold, precise structural implications of the two distinct TMH motifs and their membrane-insertion mechanism still remain obscure. Here, we show that the two TMH motifs of LLO contribute differently to maintaining the structural integrity of the toxin. While the deletion of TMH1 imposed a more serious defect, truncation of TMH2 was found to have a less severe effect on the structural integrity. Despite showing membrane-binding and oligomerization ability, the TMH2-deleted LLO variant displayed drastically abrogated pore-forming activity, presumably due to compromised membrane-insertion efficacy of the pore-forming TMH motifs. When probed for the membrane-insertion mechanism, we found slower membrane-insertion kinetics for TMH2 than for TMH1. Interestingly, deletion of TMH2 arrested membrane insertion of TMH1, thus suggesting a stringent cooperation between the two TMH motifs in regulating the pore-formation mechanism of LLO. Taken together, our study provides new mechanistic insights regarding the membrane-damaging action of LLO, in the CDC family of PFTs.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"917-927"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carboxy-Amidated AamAP1-Lys has Superior Conformational Flexibility and Accelerated Killing of Gram-Negative Bacteria.","authors":"Rosalind J Van Wyk, June C Serem, Carel B Oosthuizen, Dorothy Semenya, Miruna Serian, Christian D Lorenz, A James Mason, Megan J Bester, Anabella R M Gaspar","doi":"10.1021/acs.biochem.4c00580","DOIUrl":"10.1021/acs.biochem.4c00580","url":null,"abstract":"<p><p>C-terminal amidation of antimicrobial peptides (AMPs) is a frequent minor modification used to improve antibacterial potency, commonly ascribed to increased positive charge, protection from proteases, and a stabilized secondary structure. Although the activity of AMPs is primarily associated with the ability to penetrate bacterial membranes, hitherto the effect of amidation on this interaction has not been understood in detail. Here, we show that amidation of the scorpion-derived membranolytic peptide AamAP1-Lys produces a potent analog with faster bactericidal activity, increased membrane permeabilization, and greater Gram-negative membrane penetration associated with greater conformational flexibility. AamAP1-lys-NH₂ has improved antibiofilm activity against <i>Acinetobacter baumannii</i> and <i>Escherichia coli</i>, benefits from a two- to 3-fold selectivity improvement, and provides protection against <i>A. baumannii</i> infection in a <i>Galleria mellonella</i> burn wound model. Circular dichroism spectroscopy shows both peptides adopt α-helix conformations in the steady state. However, molecular dynamics (MD) simulations reveal that, during initial binding, AamAP1-Lys-NH₂ has greater conformation heterogeneity, with substantial polyproline-II conformation detected alongside α-helix, and penetrates the bilayer more readily than AamAP1-Lys. AamAP1-Lys-NH₂ induced membrane permeabilization of <i>A. baumannii</i> occurs only above a critical concentration with slow and weak permeabilization and slow killing occurring at its lower MIC but causes greater and faster permeabilization than AamAP1-Lys, and kills more rapidly, when applied at equal concentrations. Therefore, while the increased potency of AamAP1-Lys-NH₂ is associated with slow bactericidal killing, amidation, and the conformational flexibility it induces, affords an improvement in the AMP pharmacodynamic profile and may need to be considered to achieve improved therapeutic performance.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"841-859"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143050943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Fluctuations in the Peridinin-Chlorophyll a-Protein on the Energy Transfer: Insights from Classical and QM/MM Molecular Dynamics Simulations.","authors":"Monja Sokolov, Qiang Cui","doi":"10.1021/acs.biochem.4c00568","DOIUrl":"10.1021/acs.biochem.4c00568","url":null,"abstract":"<p><p>The peridinin-chlorophyll a-protein is a light-harvesting complex found in dinoflagellates, which has an unusually high fraction of carotenoids. The carotenoids are directly involved in the energy transfer to chlorophyll with high efficiency. The detailed mechanism of energy transfer and the roles of the protein in the process remain debated in the literature, in part because most calculations have focused on a limited number of chromophore structures. Here we investigate the magnitude of the fluctuations of the site energies of individual and coupled chromophores, as the results are essential to the understanding of experimental spectra and the energy transfer mechanism. To this end, we sampled conformations of the PCP complex by means of classical and quantum mechanical/molecular mechanical (QM/MM) molecular dynamics simulations. Subsequently we performed (supermolecular) excitation energy calculations on a statistically significant number of snapshots using TD-LC-DFT/CAM-B3LYP and the semiempirical time-dependent long-range corrected density functional tight binding (TD-LC-DFTB2) as the QM method. We observed that the magnitude of the site energy fluctuations is large compared to the differences of the site energies between the chromophores, and this also holds for the coupled chromophores. We also investigated the composition of the coupled states, the effect of coupling on the absorption spectra, as well as transition dipole moment orientations and the possibility of delocalized states with Chl a. Our study thus complements previous computational studies relying on a single structure and establishes the most prominent features of the coupled chromophores that are essential to the robustness of the energy transfer process.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"879-894"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Peptide Agonist Dissociation and Deactivation of Adhesion G-Protein-Coupled Receptors.","authors":"Keya Joshi, Yinglong Miao","doi":"10.1021/acs.biochem.4c00531","DOIUrl":"10.1021/acs.biochem.4c00531","url":null,"abstract":"<p><p>Adhesion G protein-coupled receptors (ADGRs) belong to Class B2 of GPCRs and are involved in a wide array of important physiological processes. ADGRs contain a GPCR autoproteolysis-inducing domain that is proximal to the receptor N-terminus and undergoes autoproteolysis during the biosynthesis to generate two fragments: the N-terminal fragment (NTF) and the C-terminal fragment (CTF). Dissociation of NTF reveals a tethered agonist to activate the CTF of ADGRs for G protein signaling. Synthetic peptides that mimic the tethered agonist can also activate ADGRs. However, mechanisms of peptide agonist dissociation and the deactivation of ADGRs remain poorly understood. In this study, we have performed all-atom enhanced sampling simulations using a novel protein-protein interaction Gaussian-accelerated molecular dynamics (PPI-GaMD) method on the ADGRG2-IP15 and ADGRG1-P7 complexes. The PPI-GaMD simulations captured the dissociation of the IP15 and P7 peptide agonists from their target receptors. We were able to identify important low-energy conformations of ADGRG2 and ADGRG1 in the active, intermediate, and inactive states, as well as different states of the peptide agonists IP15 and P7 during dissociation. Therefore, our PPI-GaMD simulations have revealed dynamic mechanisms of peptide agonist dissociation and deactivation of ADGRG1 and ADGRG2, which will facilitate the rational design of peptide regulators of the two receptors and other ADGRs.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"871-878"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143187572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Huntingtin Transport Complex.","authors":"Emily N P Prowse, Brooke A Turkalj, Lale Gursu, Adam G Hendricks","doi":"10.1021/acs.biochem.4c00811","DOIUrl":"10.1021/acs.biochem.4c00811","url":null,"abstract":"<p><p>A dynamic network of scaffolding molecules, adaptor proteins, and motor proteins work together to orchestrate the movement of proteins, mRNA, and vesicular cargoes. Defects in intracellular transport can often lead to neurodegeneration. Huntingtin (HTT) is a ubiquitously expressed scaffolding protein with a multitude of cellular roles, including regulating the transport of various organelles. HTT is remarkable in its ability to regulate the transport of a wide range of cargoes, including BDNF vesicles, APP vesicles, early endosomes, autophagosomes, lysosomes, and mitochondria. This interaction network allows huntingtin to control microtubule-based transport by kinesin and dynein, as well as actin-based transport by myosin VI. By forming complexes with multiple motor adaptors, huntingtin regulates a variety of cargoes and guides cargoes through the different stages of biosynthesis, signaling, and degradation. Accordingly, pathogenic polyglutamine expansions seen in Huntington's Disease (HD) dysregulate huntingtin transport complexes, resulting in defects in transport and neurodegeneration.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"760-769"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identifying Allosteric Hotspots in <i>Mycobacterium tuberculosis</i> cAMP Receptor Protein through Structural Homology.","authors":"Stephen P Dokas, Daniel K Taylor, Lydia L Good, Sanuja Mohanaraj, Rodrigo A Maillard","doi":"10.1021/acs.biochem.4c00723","DOIUrl":"10.1021/acs.biochem.4c00723","url":null,"abstract":"<p><p>Understanding the mechanisms of allosteric regulation in response to second messengers is crucial for advancing basic and applied research. This study focuses on the differential allosteric regulation by the ubiquitous signaling molecule, cAMP, in the cAMP receptor protein from <i>Escherichia coli</i> (CRP_Ecoli) and from <i>Mycobacterium tuberculosis</i> (CRP_MTB). By introducing structurally homologous mutations from allosteric hotspots previously identified in CRP_Ecoli into CRP_MTB and examining their effects on protein solution structure, stability and function, we aimed to determine the factors contributing to their differential allosteric regulation. Our results demonstrate that the mutations did not significantly alter the overall fold, assembly and thermodynamic stability of CRP_MTB, but had varying effects on cAMP binding affinity and cooperativity. Interestingly, the mutations had minimal impact on the specific binding of CRP_MTB to DNA promoter sites. However, we found that cAMP primarily reduces nonspecific CRP_MTB-DNA complexes and that the mutants largely lose this ability. Furthermore, our experiments revealed that CRP_MTB-DNA complexes serve as a nucleation point for additional binding of CRP_MTB proteins to form high-order oligomers with the DNA. Overall, our findings highlight the importance of both cAMP and DNA interactions in modulating the allosteric regulation of CRP_MTB and provide insights into the differential responses of CRP_Ecoli and CRP_MTB to cAMP.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"801-811"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frataxin Traps Low Abundance Quaternary Structure to Stimulate Human Fe-S Cluster Biosynthesis.","authors":"Seth A Cory, Cheng-Wei Lin, Shachin Patra, Steven M Havens, Christopher D Putnam, Mehdi Shirzadeh, David H Russell, David P Barondeau","doi":"10.1021/acs.biochem.4c00733","DOIUrl":"10.1021/acs.biochem.4c00733","url":null,"abstract":"<p><p>Iron-sulfur clusters are essential protein cofactors synthesized in human mitochondria by an NFS1-ISD11-ACP-ISCU2-FXN assembly complex. Surprisingly, researchers have discovered three distinct quaternary structures for cysteine desulfurase subcomplexes, which display similar interactions between NFS1-ISD11-ACP protomeric units but dramatically different dimeric interfaces between the protomers. Although the role of these different architectures is unclear, possible functions include regulating activity and promoting the biosynthesis of distinct sulfur-containing biomolecules. Here, crystallography, native ion-mobility mass spectrometry, and chromatography methods reveal the Fe-S assembly subcomplex exists as an equilibrium mixture of these different quaternary structures. Isotope labeling and native mass spectrometry experiments show that the NFS1-ISD11-ACP complexes disassemble into protomers, which can then undergo exchange reactions and dimerize to reform native complexes. Single crystals isolated in distinct architectures have the same activity profile and activation by the Friedreich's ataxia (FRDA) protein frataxin (FXN) when rinsed and dissolved in assay buffer. These results suggest FXN functions as a \"molecular lock\" and shifts the equilibrium toward one of the architectures to stimulate the cysteine desulfurase activity and promote iron-sulfur cluster biosynthesis. An NFS1-designed variant similarly shifts the equilibrium and partially replaces FXN in activating the complex. We propose that eukaryotic cysteine desulfurases are unusual members of the morpheein class of enzymes that control their activity through their oligomeric state. Overall, the findings support architectural switching as a regulatory mechanism linked to FXN activation of the human Fe-S cluster biosynthetic complex and provide new opportunities for therapeutic interventions of the fatal neurodegenerative disease FRDA.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"903-916"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11840927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of Molecular Interactions between the G3BP1 Stress Granule Host Protein and the Nucleocapsid (NTD-N) Protein Impedes SARS-CoV-2 Virus Replication.","authors":"Preeti Dhaka, Ankur Singh, Sanketkumar Nehul, Shweta Choudhary, Prasan Kumar Panda, Gaurav Kumar Sharma, Pravindra Kumar, Shailly Tomar","doi":"10.1021/acs.biochem.4c00536","DOIUrl":"10.1021/acs.biochem.4c00536","url":null,"abstract":"<p><p>The Ras GTPase-activating protein SH3-domain-binding protein 1 (G3BP1) serves as a formidable barrier to viral replication by generating stress granules (SGs) in response to viral infections. Interestingly, viruses, including SARS-CoV-2, have evolved defensive mechanisms to hijack SG proteins like G3BP1 for the dissipation of SGs that lead to the evasion of the host's immune responses. Previous research has demonstrated that the interaction between the NTF2-like domain of G3BP1 (G3BP1_NTF-2) and the intrinsically disordered N-terminal domain (NTD-N_1-25) of the N-protein plays a crucial role in regulating viral replication and pathogenicity. Interestingly, the current study identified an additional upstream stretch of residues (128KDGIIWVATEG138) (N_128-138) within the N-terminal domain of the N-protein (NTD-N_41-174) that also forms molecular contacts with the G3BP1 protein, as revealed through <i>in silico</i> analysis, site-directed mutagenesis, and biochemical analysis. Remarkably, WIN-62577, and fluspirilene, the small molecules targeting the conserved peptide-binding pocket in G3BP1_NTF-2, not only disrupted the protein-protein interactions (PPIs) between NTD-N_41-174 and G3BP1_NTF-2 but also exhibited significant antiviral efficacy against SARS-CoV-2 replication with EC₅₀ values of ∼1.8 and ∼1.3 μM, respectively. The findings of this study, validated by biophysical thermodynamics and biochemical investigations, advance the potential of developing therapeutics targeting the SG host protein against SARS-CoV-2, which may also serve as a broad-spectrum antiviral target.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":"823-840"},"PeriodicalIF":2.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}