Journal of Molecular Biology最新文献_第7页

Search for Specific Inhibitors Targeting Type IA Topoisomerases 寻找针对IA型拓扑异构酶的特异性抑制剂。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-07-16 DOI: 10.1016/j.jmb.2025.169349

Somaia Haque Chadni , Shomita Ferdous , Yuk-Ching Tse-Dinh

{"title":"Search for Specific Inhibitors Targeting Type IA Topoisomerases","authors":"Somaia Haque Chadni , Shomita Ferdous , Yuk-Ching Tse-Dinh","doi":"10.1016/j.jmb.2025.169349","DOIUrl":"10.1016/j.jmb.2025.169349","url":null,"abstract":"<div><div>The type IA topoisomerase subfamily includes bacterial topoisomerase I and topoisomerase III encoded by <em>topA</em> and <em>topB</em> genes, reverse gyrase found in thermophilic bacteria and archaea, as well as eukaryotic topoisomerase III. Type IA topoisomerases also act on RNA as substrate. Important functions in neurological development have been demonstrated for human TOP3B. Type IA topoisomerase present in all bacterial pathogens should be a novel target that can be utilized for the discovery of new antibacterial agents. Naturally produced bacterial toxins have been shown to inhibit cell growth by targeting topoisomerase I. Topoisomerase III in human and other eukaryotes could potentially also be targeted for treatment of cancer and viral or parasitic infections. Docking, machine-learning, enzyme or cell-based screening campaigns have identified compounds that can inhibit the catalytic activity of type IA topoisomerases, or poisons that can trap the covalent complex of the targeted type IA topoisomerase. Small molecule inhibitors identified thus far for bacterial topoisomerase I or human TOP3B have not been viable candidates as drug leads mostly due to lack of sufficient potency and selectivity. The barriers for obtaining better inhibitors include the lack of an X-ray or cryo-EM structure of topoisomerase-ligand complex and mutations in the topoisomerase gene that can confirm the topoisomerase as primary cellular target. Well-designed combination of virtual and experiment screening to explore large chemical space in future studies may improve the likelihood of success for identifying small molecule inhibitors of type IA topoisomerases that can form specific protein–ligand complexes amenable for structure determination.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 5","pages":"Article 169349"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144666754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Topoisomerase II Mutations in Cancer: Structural Impact and Drug Response in High-grade Serous Ovarian Carcinoma 癌症中的DNA拓扑异构酶ii突变：高级别浆液性卵巢癌的结构影响和药物反应。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-08-11 DOI: 10.1016/j.jmb.2025.169384

Viola Mazzoleni , Amélie Boichard , Valérie Lamour

{"title":"DNA Topoisomerase II Mutations in Cancer: Structural Impact and Drug Response in High-grade Serous Ovarian Carcinoma","authors":"Viola Mazzoleni , Amélie Boichard , Valérie Lamour","doi":"10.1016/j.jmb.2025.169384","DOIUrl":"10.1016/j.jmb.2025.169384","url":null,"abstract":"<div><div>Topoisomerases are essential enzymes that resolve DNA topological stress during replication and transcription. In mammalian cells, the two isoforms, TOP2A and TOP2B, differ in expression profiles and functions. TOP2A is a key regulator of cell division, mainly expressed in rapidly dividing cells, such as cancer cells, and is therefore the primary target of several chemotherapeutic molecules. In contrast, TOP2B is ubiquitously expressed in both dividing and non-dividing cells and is not directly implicated in tumorigenesis. Despite their functional differences, the high homology of the two isoforms contributes to unwanted off-target effects of TOP2-directed therapies, sometimes leading to secondary cancer. Both isoforms can harbor naturally occurring or cancer-associated point mutations, which could confer altered sensitivity or resistance to chemotherapy agents. Using data from cancer genomic databases, we analyzed hotspot mutations of both isoforms found in human tumors and conducted a molecular analysis based on structural and functional data. We identified TOP2 variants in high-grade serous ovarian carcinoma, a malignancy frequently treated with TOP2-targeting agents, such as doxorubicin or etoposide. Our analysis emphasizes the importance of modeling somatic mutations to assess enzyme conformation and therapeutic response. Additionally, this review provides insights that underline the potential value of including <em>TOP2A</em> and <em>TOP2B</em> in companion diagnostic gene panels used in personalized oncology, notably in cancers where TOP2-directed agents are part of the standard therapy.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 5","pages":"Article 169384"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular Determinants of Selective and High-affinity Binding of the Scaffold Protein PDZK1 to the Urate Transporter URAT1 支架蛋白PDZK1与尿酸转运蛋白URAT1选择性和高亲和力结合的分子决定因素。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-12-24 DOI: 10.1016/j.jmb.2025.169615

Evgeny V. Mymrikov , Christophe Wirth , Jonas I. Heinicke , Julian Goll , Bianca A. Kern , Christoph Steck , Anastasiia K. Iaroslavtceva , Tobias Mühlethaler , Anna Köttgen , Carola Hunte

{"title":"Molecular Determinants of Selective and High-affinity Binding of the Scaffold Protein PDZK1 to the Urate Transporter URAT1","authors":"Evgeny V. Mymrikov , Christophe Wirth , Jonas I. Heinicke , Julian Goll , Bianca A. Kern , Christoph Steck , Anastasiia K. Iaroslavtceva , Tobias Mühlethaler , Anna Köttgen , Carola Hunte","doi":"10.1016/j.jmb.2025.169615","DOIUrl":"10.1016/j.jmb.2025.169615","url":null,"abstract":"<div><div>The renal solute carrier URAT1 (SLC22A12) is essential for urate homeostasis, with loss-of-function linked to renal hypouricemia, nephrolithiasis and lower gout risk. URAT1 function depends on binding the multi-PDZ domain scaffold protein PDZK1 (NHERF3), with a similar role suggested for the related NHERF1. The molecular basis of these interactions remains poorly understood. Using fluorescence anisotropy, we show that full-length human PDZK1 binds the C-terminal peptide of URAT1 with high affinity (<em>K</em><sub>D</sub> 170 nM), unlike NHERF1 (<em>K</em><sub>D</sub> > 70 µM). The PDZ1 domain of PDZK1 alone is sufficient for high-affinity binding (<em>K</em><sub>D</sub> 160 nM), while PDZ4 provides a secondary site (<em>K</em><sub>D</sub> 1.35 µM), with both interactions characterized by rapid kinetics. Gel filtration shows that PDZK1 can bind two URAT1 peptides. X-ray structures of individual PDZ domains from PDZK1 and NHERF1 complexed with the URAT1 peptide reveal the underlying molecular basis for selectivity and broad affinity range. Murine Pdzk1 and Nherf1 bind Urat1 with high affinity indicating species-specific interactions. These data provide insights into URAT1 regulation by PDZ scaffold proteins with relevance for understanding urate homeostasis regulation and related disorders.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 5","pages":"Article 169615"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BusR is a Bifunctional Transcription Factor Coordinating Both Osmotic Response and Amino Sugar Metabolism in Streptococcus mutans BusR是一种双功能转录因子，在变形链球菌中协调渗透反应和氨基糖代谢。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-03-01 Epub Date: 2026-01-14 DOI: 10.1016/j.jmb.2026.169640

Xin Li , Nan Liu , Kaiyu Gao , Carina Muyao Gu , Zhihao Cui , Kundi Zhang , Sujuan Xu , Lichuan Gu

{"title":"BusR is a Bifunctional Transcription Factor Coordinating Both Osmotic Response and Amino Sugar Metabolism in Streptococcus mutans","authors":"Xin Li , Nan Liu , Kaiyu Gao , Carina Muyao Gu , Zhihao Cui , Kundi Zhang , Sujuan Xu , Lichuan Gu","doi":"10.1016/j.jmb.2026.169640","DOIUrl":"10.1016/j.jmb.2026.169640","url":null,"abstract":"<div><div><em>Streptococcus mutans,</em> the major causative agent of dental plaque and caries, maintains osmotic balance under hyperosmotic conditions by transporting glycine betaine into the cytoplasm via the BusAB transporter system. This mechanism is coordinated by the c-di-AMP-responsive transcriptional regulator BusR, which represses <em>busAB</em> expression in the absence of osmotic stress. In this study, we systematically characterized the function of BusR in <em>S. mutans</em> UA159. Our experiments showed that deletion of <em>busR</em> resulted not only in high expression of <em>busAB</em> but also in upregulated GlcNAc metabolic genes, specifically <em>nagA/nagB</em> and <em>glmS</em>, which are known to be regulated by transcriptional regulator NagR. The Δ<em>busR</em> strain utilized GlcNAc as a nutrient more efficiently and exhibited a faster growth rate than the wild-type strain. Combined with results from further experimentation, this suggests that, BusR assumes a dual regulatory role under high-osmolarity conditions: it relieves repression of <em>busAB</em> to increase the transport of the osmoprotectant betaine into cytoplasm, and cooperates with NagR to regulate amino sugar metabolism by regulating the transcription of <em>nagA/nagB</em> and <em>glmS</em>. Consistent with the molecular ruler mechanism previously described for BusR homologs from <em>Streptococcus agalactiae</em>, we observe a similar structural basis that enables BusR to mediate precise, c-di-AMP–dependent modulation of gene transcription. This coordinated regulation of osmoprotection and amino sugar metabolism by BusR may give <em>S. mutans</em> a significant advantage for dealing with osmotic stress within the oral environment.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 5","pages":"Article 169640"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

DNA Topoisomerase VI: Structure, Function and Mechanism DNA拓扑异构酶VI：结构、功能和机制。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-03-01 Epub Date: 2025-10-22 DOI: 10.1016/j.jmb.2025.169492

Adam M.B. Allen , Shannon J. McKie , Christian G. Noble , Anthony Maxwell

{"title":"DNA Topoisomerase VI: Structure, Function and Mechanism","authors":"Adam M.B. Allen , Shannon J. McKie , Christian G. Noble , Anthony Maxwell","doi":"10.1016/j.jmb.2025.169492","DOIUrl":"10.1016/j.jmb.2025.169492","url":null,"abstract":"<div><div>DNA topoisomerase VI (topo VI) is a type IIB topoisomerase that was originally found in archaea but later found in plants and some other eukaryotes and certain bacteria; claims that it is present in plasmodial parasites have yet to be substantiated. In plants it appears to have an essential role in endoreduplication, but its role in other organisms is less clear. Although topo VI is evolutionarily related to type IIA topoisomerases, it shows a different domain organisation and lacks an exit gate (C gate). Crystal structures of topo VI consolidate these distinctions and show protein cavities and subunit interfaces that are consistent with a double-strand passage mechanism. Single-molecule and ensemble measurements of topo VI reactions show that the rate of DNA relaxation is much slower than with its IIA counterparts, but that it shows a preference for decatenation over relaxation reactions. Radicicol, a known inhibitor of human topo II, also inhibits some topo VI enzymes, and recent drug screens have identified further compounds. Topo VI is ripe for exploitation as a target for herbicides and potentially for antibacterials.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 5","pages":"Article 169492"},"PeriodicalIF":4.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145367246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Repair of Single-Stranded Breaks in Hyperthermophilic DNA 超嗜热DNA单链断裂的修复。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-02-15 Epub Date: 2025-11-26 DOI: 10.1016/j.jmb.2025.169565

Alexander Vologodskii

引用次数: 0

Electrolyte–amino acid interplay in the stability mechanisms of halophilic proteins 电解质-氨基酸在嗜盐蛋白稳定性机制中的相互作用。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-02-15 Epub Date: 2026-01-23 DOI: 10.1016/j.jmb.2026.169651

Xiaoci Hu, Ana Vila Verde

{"title":"Electrolyte–amino acid interplay in the stability mechanisms of halophilic proteins","authors":"Xiaoci Hu, Ana Vila Verde","doi":"10.1016/j.jmb.2026.169651","DOIUrl":"10.1016/j.jmb.2026.169651","url":null,"abstract":"<div><div>Proteins of halophilic microorganisms thrive in high-salt environments. Compared to mesophilic proteins, they are enriched in acidic residues and small polar/apolar amino acids while being depleted in large hydrophobic residues, features that strongly influence their structure and stability. Here we critically examine experimental and computational studies investigating the mechanistic connection between the halophilic proteome and thermodynamic stability of halophilic proteins as a function of salt concentration. A defining feature of halophilic proteins is their highly negative surface charge, arising from abundant acidic residues. Some studies suggest this property is essential to ensure proteins remain folded at high salt concentrations, while others argue that a net negative protein charge might always be destabilizing. Alternative views propose that reducing solvent-exposed hydrophobic surface area is more critical than charge for stability at high salt concentrations. Advancing our understanding on this topic will require addressing multiple knowledge gaps. The unfolded states of both protein classes remain poorly characterized, leaving differences in local and non-local entropy contributions between the folded and the unfolded states to salt-dependent protein stability largely unexplored. Packing, cation-carbonyl and hydrophobic SASA differences between both protein classes are also insufficiently quantified. Atomistic molecular dynamics simulations with explicit solvent can advantageously be used to investigate these issues. Simultaneously, theoretical frameworks to understand how small perturbations in protein composition impact its stability as a function of salt concentration need to be expanded to include these contributions, which to date have been neglected, to fully understand how a halophilic proteome impacts salt-dependent stability.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 4","pages":"Article 169651"},"PeriodicalIF":4.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146045738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Learning About Protein Stability and Functional Activity From Ancestral Reconstruction 从祖先重建中了解蛋白质的稳定性和功能活性。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-02-15 Epub Date: 2025-09-11 DOI: 10.1016/j.jmb.2025.169435

Satoshi Akanuma

{"title":"Learning About Protein Stability and Functional Activity From Ancestral Reconstruction","authors":"Satoshi Akanuma","doi":"10.1016/j.jmb.2025.169435","DOIUrl":"10.1016/j.jmb.2025.169435","url":null,"abstract":"<div><div>Understanding how proteins have evolved to adapt their stability and function to changing temperatures remains a central question in molecular biology. While structural analyses, site-directed mutagenesis, and directed evolution have yielded valuable insights, ancestral sequence reconstruction (ASR) has recently emerged as a powerful tool for addressing the drivers behind protein evolution. Specifically, by enabling the inference and experimental characterization of reconstructed ancient proteins, ASR provides unique perspectives on the molecular mechanisms underlying both thermostability and low-temperature-adaptation. This review outlines the historical development of research on protein temperature adaptation and highlights the role of ASR in advancing the field. Selected case studies illustrate how ASR has uncovered structural and dynamic features associated with extreme thermostability or enhanced activity at low temperatures. Common sources of uncertainty in ASR and how they can be addressed are also discussed. Finally, the broader potential of ASR is described, both for elucidating early evolutionary processes and for guiding the design of enzymes useful for industrial applications.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 4","pages":"Article 169435"},"PeriodicalIF":4.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of Horizontal Gene Transfer on Adaptations to Extreme Environments 水平基因转移对极端环境适应的影响。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-02-15 Epub Date: 2025-08-21 DOI: 10.1016/j.jmb.2025.169403

Olga Zhaxybayeva , Camilla L. Nesbø

{"title":"Impact of Horizontal Gene Transfer on Adaptations to Extreme Environments","authors":"Olga Zhaxybayeva , Camilla L. Nesbø","doi":"10.1016/j.jmb.2025.169403","DOIUrl":"10.1016/j.jmb.2025.169403","url":null,"abstract":"<div><div>Horizontal (or lateral) gene transfer – an acquisition of genetic material not associated with the organismal reproduction – is known to alter genomes of most, if not all, living organisms. There is mounting evidence for the importance of gene exchange in organismal adaptations to new or changing environmental conditions. In comparison to accumulation of <em>de novo</em> mutations, acquisition of a gene already beneficial in the environment is fast and less costly, and thus an advantageous, way to adjust to survival and growth in new conditions. Adaptation to extreme environments at the boundaries of habitat conditions beyond which cellular integrity, metabolism and growth are not possible, is not an exception. Here we review the impact of horizontal gene transfer on organismal adaptations to natural and human-made extreme environments<em>.</em> This includes thermophiles living at high temperatures, psychrophiles found at low temperatures, acidophiles inhabiting high acidity environments, alkaliphiles thriving at high pH, halophiles found in high salt environments, xerophiles that can tolerate extremely low water availability, oligotrophes thriving at low nutrient availability, piezophiles inhabiting high pressure environments, and organisms that can withstand high levels of ionizing radiation. We also discuss the challenges and future directions for deciphering genetic determinants and horizontal gene transfer events of extremophiles’ adaptations.</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 4","pages":"Article 169403"},"PeriodicalIF":4.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

On the Relationship Between Protein Stability, Thermostability, and Allosteric Signaling 蛋白质稳定性、热稳定性和变构信号之间的关系。

IF 4.5 2区生物学

Journal of Molecular Biology Pub Date : 2026-02-15 Epub Date: 2025-11-10 DOI: 10.1016/j.jmb.2025.169537

Raechell , Wei-Ven Tee , Bingxue Dong , Enrico Guarnera , Igor N. Berezovsky

{"title":"On the Relationship Between Protein Stability, Thermostability, and Allosteric Signaling","authors":"Raechell , Wei-Ven Tee , Bingxue Dong , Enrico Guarnera , Igor N. Berezovsky","doi":"10.1016/j.jmb.2025.169537","DOIUrl":"10.1016/j.jmb.2025.169537","url":null,"abstract":"<div><div>The thermodynamic stability of proteins and regulation of their functional activity can be described within the energy landscape framework, where the former is provided by a unique native conformational ensemble separated by an energy gap from misfolded structures, and the latter is based on conformational transitions between structural states in the native ensemble. This work investigates the relationship between fundamentals of structural stability and dynamics-driven allosteric regulation. We describe here general proteomic trends and fold/function-specific determinants of protein stability. The intricate relationship between stability and allostery has been observed, showing how requirements on stability and thermal adaptation drive and shape the protein’s “structural platform”, while complementary sequence-structure determinants control the allosteric signaling and regulation. We illustrate our findings using four groups of proteins – inorganic pyrophosphatase and β-glucosidase representing hydrolases, the CheY signaling protein, and adenylate kinase – obtained from host organisms spanning from psychrophiles to hyperthermophiles. We also show that allosteric effects of mutations in adenylate kinase account for experimentally observed changes in organismal fitness expressed in bacterial growth rates. Epistasis arising from the effects of these mutations is another important phenomenon, resulting in unexpected non-additive changes in fitness that could not be explained by the stability changes alone. The findings in this work and options for further investigations of the stability-signaling relationship are provided by the sequence-dependent model of allostery employed here and implemented in AlloSigMA 3 – the latest update of our AlloSigMA web-server (<span><span>https://allosigma.bii.a-star.edu.sg</span><svg><path></path></svg></span>).</div></div>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":"438 4","pages":"Article 169537"},"PeriodicalIF":4.5,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0