Biological Chemistry最新文献

Functional role of the second messengers PtdIns(3,4,5)P₃ and PtdIns(3,4)P₂ in carcinogenesis. 第二信使PtdIns(3,4,5)P3和PtdIns(3,4)P2在癌变中的功能作用。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-10-20 DOI: 10.1515/hsz-2026-0181

Nina Nelson, Manfred Jücker

引用次数: 0

Structural basis of serine protease inhibition by antibodies from biased Fab phage-display libraries. 偏倚Fab噬菌体展示文库抗体抑制丝氨酸蛋白酶的结构基础。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-10-07 DOI: 10.1515/hsz-2026-0121

Kyle J Anderson, Melody S Lee, Natalia Sevillano, Gang Chen, Michael J Hornsby, Sachdev S Sidhu, Charles S Craik

{"title":"Structural basis of serine protease inhibition by antibodies from biased Fab phage-display libraries.","authors":"Kyle J Anderson, Melody S Lee, Natalia Sevillano, Gang Chen, Michael J Hornsby, Sachdev S Sidhu, Charles S Craik","doi":"10.1515/hsz-2026-0121","DOIUrl":"10.1515/hsz-2026-0121","url":null,"abstract":"Biased Fab phage-display libraries were designed to determine whether inhibitory CDR H3 motifs from potent anti-matriptase antibodies could be transferred to target homologous serine proteases. Using reverse-binding and substrate-like H3 motifs from parental clones A11 and E2 as templates, six synthetic libraries with 1010 diversity were constructed. Selection against matriptase identified 16 inhibitors with sub-100 nM potency, representing 100,000-fold improvement over circularized H3 loops alone. Selection against TMPRSS2, a serine protease implicated in viral entry and prostate cancer with 43 % sequence identity to matriptase, yielded binders with micromolar inhibitory potency. Selection against urokinase plasminogen activator (uPA, 35 % identity) identified binders that adopted a substrate-like CDR H3 binding mode in our structural models. Across all reference structures, including the separately identified uPA inhibitor AB2 (PDB: 9PYF, deposited with this work), benchmarking of five co-folding methods and rigid-body docking showed that co-folding consistently achieved acceptable to high quality DockQ scores, outperforming traditional docking and capturing the recognition of key active site determinants. Ensemble predictions of mutational binding energy changes (ΔΔG) using these models identified key paratope-epitope interactions, with predictions validated through mutagenesis. This work establishes a framework integrating biased antibody libraries with computational structure prediction and analysis for targeting conserved protease epitopes.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149134534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Trends in optimizing antibacterial cationic amphiphiles. 抗菌阳离子两亲体优化研究进展。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-10-05 DOI: 10.1515/hsz-2026-0159

Oladapo J Olaosebikan, Jonathan O Babalola, Leonhard H Urner

{"title":"Trends in optimizing antibacterial cationic amphiphiles.","authors":"Oladapo J Olaosebikan, Jonathan O Babalola, Leonhard H Urner","doi":"10.1515/hsz-2026-0159","DOIUrl":"https://doi.org/10.1515/hsz-2026-0159","url":null,"abstract":"Cationic amphiphiles are investigated as antibacterials, yet their potential is often limited by host-cell toxicity. Bacterial and mammalian membranes share core physicochemical features that promote interactions with cationic amphiphiles. Selectivity is realistically understood as a relative property window. This review summarizes recent trends in the design of antibacterial cationic amphiphiles, focusing on quaternary ammonium compounds, lipopeptides and dendritic amphiphiles. Across these structurally diverse compound classes, tuning charge density, hydrophobicity, degradability, lipid selectivity, and supramolecular properties emerge as design approaches to improve antibacterial potency and reduce toxicity. Recent developments exploit bacterial lipids and lipid membrane surfaces as targets and employ design strategies to improve selectivity, such as multivalent presentation of cationic groups, optimization of membrane insertion, and combinations of membrane-targeting building blocks. Cationic amphiphiles inserting into bacterial membranes can induce permeabilization, dissipation of the proton motive force, and disruption of energy homeostasis, suggesting these processes represent a common mechanistic framework linking physical membrane damage to antibacterial activity. Complementing phenotypic screenings by mechanistic studies and concentration-dependent mode-of-action profiling across compound series is a promising future direction. Understanding how molecular structure governs membrane interactions and bacterial physiology will support the development of next-generation cationic amphiphiles with improved potency, selectivity and translational potential.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sequestosome 1 (SQSTM1/p62) at the nexus of genome integrity maintenance, proteostasis regulation and organellar homeostasis. Sequestosome 1 （SQSTM1/p62）在基因组完整性维持、蛋白质平衡调节和细胞器稳态中的作用。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-09-29 DOI: 10.1515/hsz-2026-0146

Celina Hirschelmann, Prince Saforo Amponsah

引用次数: 0

Phytochemical characterization, thermal stability, antimutagenic, antifungal and antibacterial potential of O. sanctum against sewage water borne antibiotic-resistant bacteria. 植物化学性质、热稳定性、抗诱变、抗真菌和抗菌潜力。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-09-25 DOI: 10.1515/hsz-2026-0165

Abhishek Kumar, Ashutosh Singh, Parul Verma, Sajid Ali, Ritu Chauhan, Asadjon Kambarov, Rano Toshkodirova, Makhmudjon Mirsaidov

{"title":"Phytochemical characterization, thermal stability, antimutagenic, antifungal and antibacterial potential of O. sanctum against sewage water borne antibiotic-resistant bacteria.","authors":"Abhishek Kumar, Ashutosh Singh, Parul Verma, Sajid Ali, Ritu Chauhan, Asadjon Kambarov, Rano Toshkodirova, Makhmudjon Mirsaidov","doi":"10.1515/hsz-2026-0165","DOIUrl":"https://doi.org/10.1515/hsz-2026-0165","url":null,"abstract":"This study evaluated the phytochemical composition, antioxidant, antimutagenic, antifungal and antibacterial activities of O. sanctum leaf extracts, with particular focus on sewage water-borne antibiotic-resistant bacteria. Methanolic, ethyl acetate and hexane extracts were prepared and evaluated for phytochemical constituents, total phenolic and flavonoid contents and antioxidant activity. The methanolic extract (OsLME) showed the highest phenolic (43.15 ± 0.52 mg GAE g-1) and flavonoid (19.34 ± 0.36 mg RE g-1) contents and showed the highest antioxidant activity (89.12 ± 1.8 % inhibition at 4,000 μg mL-1). OsLME did not show mutagenic activity in the tested Salmonella typhimurium strains and showed antimutagenic activity against known mutagens. It also showed the highest antifungal activity against Candida albicans (22.11 ± 4.2 mm) and antibacterial activity against antibiotic-resistant bacteria, with the lowest MIC of 250 μg mL-1 against Pseudomonas aeruginosa. Thermal stability analysis showed a gradual reduction in bioactivity, particularly at 50 °C. The findings indicate that O. sanctum, especially its methanolic leaf extract, is a promising source of bioactive compounds with antioxidant and antimicrobial potential against antibiotic-resistant bacteria.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149036216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ACOD1-dependent succinate signalling acts as a metabolic checkpoint for osteoclast differentiation. acod1依赖性琥珀酸盐信号作为破骨细胞分化的代谢检查点。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-09-07 DOI: 10.1515/hsz-2026-0168

Yue Gao, Genyang Xin, Elisabeth Seebach, Dominik Schaack, Markus A Weigand, Katharina F Kubatzky

{"title":"ACOD1-dependent succinate signalling acts as a metabolic checkpoint for osteoclast differentiation.","authors":"Yue Gao, Genyang Xin, Elisabeth Seebach, Dominik Schaack, Markus A Weigand, Katharina F Kubatzky","doi":"10.1515/hsz-2026-0168","DOIUrl":"https://doi.org/10.1515/hsz-2026-0168","url":null,"abstract":"Immune cells undergo metabolic reprogramming in response to inflammatory stimuli. The immuneresponsive gene 1 (Irg1) encodes aconitate decarboxylase (ACOD1), which generates itaconate from cis-aconitate in the TCA cycle. Itaconate inhibits succinate dehydrogenase, resulting in succinate accumulation. Stable ACOD1 overexpression in RAW264.7 cells shifted cellular metabolism towards glycolysis, as indicated by enhanced mTOR activation, increased 4E-BP1 phosphorylation, and reduced ATP levels. ACOD1 cells displayed impaired osteoclastogenesis with reduced expression of osteoclast-associated genes and fewer TRAP-positive multinucleated osteoclasts. Unexpectedly, NFATc1 was constitutively present in the nucleus of untreated ACOD1 cells, resulting in residual NFAT activity and induction of inflammatory genes. Upon RANKL stimulation, these pre-activated cells showed delayed osteoclastogenic signalling accompanied by sustained expression of the transcriptional repressors BCL6, MafB, and IRF8. Using a GPR91 antagonist and a Gαq inhibitor, we demonstrate that extracellular succinate activates NFATc1 via GPR91-Gαq signalling. RNA sequencing further revealed that ACOD1 overexpression promotes an innate immune transcriptional program rather than osteoclast differentiation. Together, our findings identify succinate-GPR91 signalling as a regulator of the transition between inflammatory activation and osteoclastogenesis.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148890852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cytosolic Fe/S protein biogenesis: a crossroads of Fe/S cluster machineries. 胞质铁/硫蛋白生物发生：铁/硫簇机制的十字路口。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-28 DOI: 10.1515/hsz-2026-0144

Joseph J Braymer

{"title":"Cytosolic Fe/S protein biogenesis: a crossroads of Fe/S cluster machineries.","authors":"Joseph J Braymer","doi":"10.1515/hsz-2026-0144","DOIUrl":"https://doi.org/10.1515/hsz-2026-0144","url":null,"abstract":"Iron-sulfur (Fe/S) clusters are essential inorganic cofactors required for nearly all organisms. These cofactors do not spontaneously form in cells or on proteins; they require at least one of six dedicated Fe/S protein biogenesis pathways. The eukaryotic cytosol is an intriguing cellular compartment for Fe/S protein biogenesis because genetic evidence across the eukaryotic supergroups suggests the unique occurrence of multiple, interconnected pathways being capable of fulfilling the quota of Fe/S clusters in the cytosol and nucleus. The reliance of multiple pathways for cytosolic and nuclear Fe/S protein biogenesis was first established by genetic studies in the yeast, human, and plant model organisms, which demonstrated the essentiality of mitochondrial Fe/S protein biogenesis in supplying an exported substrate to the cytosol. With the great expansion of genomic data, we have learned that other organisms have replaced the essential mitochondrial system with other Fe/S biogenesis proteins stemming from prokaryotes. Studies have demonstrated that the rewiring of cytosolic Fe/S protein biogenesis can also facilitate the reductive evolution of mitochondria and even lead to complete loss of the organelle in some organisms. This review provides an updated overview of how these differing Fe/S protein biogenesis pathways intersect and the corresponding mechanistic considerations.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural biology of retron-mediated immunity against phage. 逆转录酶介导的噬菌体免疫的结构生物学。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-28 DOI: 10.1515/hsz-2026-0145

Monika Jasnauskaitė, Patrick Pausch

{"title":"Structural biology of retron-mediated immunity against phage.","authors":"Monika Jasnauskaitė, Patrick Pausch","doi":"10.1515/hsz-2026-0145","DOIUrl":"https://doi.org/10.1515/hsz-2026-0145","url":null,"abstract":"Retrons recently emerged as widespread anti-phage systems in which a dedicated reverse transcriptase (RT) produces multicopy single-stranded DNA (msDNA) that regulates associated effector proteins. Once regarded as peculiar retroelements of unknown function, retrons are now understood to operate as modular defense platforms in which the RT-msDNA module maintains nucleases, hydrolases or other effector domains in an inactive state until a phage-trigger perturbs the complex. Current biochemical and cryo-EM structural studies across different retron types have begun to define a unifying mechanism for retron-mediated immunity. Despite substantial variation in architecture and effector types, these studies converge on a common principle: msDNA acts as a structural and functional hub that scaffolds multimeric assemblies, occludes catalytic sites or stabilizes inactive effector conformations. Phage infection is sensed through perturbation of the msDNA, including cleavage, modification or binding by phage-encoded factors, thereby activating the effector to trigger an immune response. Here, we discuss recent structural and mechanistic advances of retron immune systems. We detail how distinct retron types deploy different effectors and phage-factor-sensing strategies while preserving a shared msDNA-centered regulatory paradigm. We further place retrons in the broader landscape of bacterial defense, comparing their regulatory logic with that of toxin-antitoxin modules and other immune systems.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The prokaryotic lipid divide: how strict is it? 原核生物脂质分裂：有多严格？

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-26 DOI: 10.1515/hsz-2026-0149

Philipp Rieche, Lena Elisa Hebel, Marten Exterkate

引用次数: 0

Structural basis for the procoagulant activity of Staphylococcus aureus staphylocoagulase. 金黄色葡萄球菌葡萄凝固酶促凝活性的结构基础。

IF 2.5 4区生物学

Biological Chemistry Pub Date : 2026-08-20 DOI: 10.1515/hsz-2025-0253

Pablo Fuentes-Prior, Ashoka A Maddur, Peter Panizzi, David Gailani, Ingrid M Verhamme

{"title":"Structural basis for the procoagulant activity of Staphylococcus aureus staphylocoagulase.","authors":"Pablo Fuentes-Prior, Ashoka A Maddur, Peter Panizzi, David Gailani, Ingrid M Verhamme","doi":"10.1515/hsz-2025-0253","DOIUrl":"10.1515/hsz-2025-0253","url":null,"abstract":"Staphylocoagulase (SC), a crucial virulence protein secreted by several strains of the major pathogen Staphylococcus aureus, functions as a potent inducer of blood clotting. SC binds its zymogen target, prothrombin (ProT) with subnanomolar affinity, allosterically inducing a thrombin-like active site in the bound zymogen. The resulting SC·(Pro)T* active complexes effectively convert fibrinogen (Fbg) into clot-forming fibrin (Fbn). We previously reported crystal structures of the N-terminal SC domains, responsible for ProT binding and activation, and characterized the mechanism of cofactor-induced zymogen activation in detail. However, the lack of three-dimensional (3D) structures for the C-terminal SC region has hampered a complete understanding of its role in Fbg recognition and cleavage. Here, we present and discuss 3D models of the Fbg-binding SC region. Our results suggest that the major C-terminal domain of SC folds into a single-layer β-sheet structurally similar to the membrane occupation and recognition nexus (MORN) family of tandem repeats. We further propose a folding pathway for this C-terminal SC region that is contingent upon the presence of its substrate, Fbg. These structural and mechanistic insights are critical for understanding SC-mediated fibrin generation, which is highly relevant to heart valve vegetations and biofilm formation during S. aureus infection.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13605537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148787859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0