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Phosphoric acid salts of amino acids as a source of oligopeptides on the early Earth 作为早期地球上寡肽来源的氨基酸磷酸盐。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-22 DOI: 10.1038/s42004-024-01264-6
Judit E. Šponer, Rémi Coulon, Michal Otyepka, Jiří Šponer, Alexander F. Siegle, Oliver Trapp, Katarzyna Ślepokura, Zbyněk Zdráhal, Ondrej Šedo
Because of their unique proton-conductivity, chains of phosphoric acid molecules are excellent proton-transfer catalysts. Here we demonstrate that this property could have been exploited for the prebiotic synthesis of the first oligopeptide sequences on our planet. Our results suggest that drying highly diluted solutions containing amino acids (like glycine, histidine and arginine) and phosphates in comparable concentrations at elevated temperatures (ca. 80 °C) in an acidic environment could lead to the accumulation of amino acid:phosphoric acid crystalline salts. Subsequent heating of these materials at 100 °C for 1–3 days results in the formation of oligoglycines consisting of up to 24 monomeric units, while arginine and histidine form shorter oligomers (up to trimers) only. Overall, our results suggest that combining the catalytic effect of phosphate chains with the crystalline order present in amino acid:phosphoric acid salts represents a viable solution that could be utilized to generate the first oligopeptide sequences in a mild acidic hydrothermal field scenario. Further, we propose that crystallization could help overcoming cyclic oligomer formation that is a generally known bottleneck of prebiotic polymerization processes preventing further chain growth. Phosphates are fundamental building blocks of ribonucleic acids and excellent catalysts for proton transfer reactions. Here, the authors report that the combination of the catalytic effect of phosphates with the entropic effect of crystallization can be exploited to facilitate formation of oligopeptides from the crystalline salts of phosphoric acid with amino acids under mild conditions.
由于其独特的质子传导性,磷酸分子链是极好的质子转移催化剂。在这里,我们证明了这一特性可用于地球上第一个寡肽序列的前生物合成。我们的研究结果表明,在酸性环境中,将含有氨基酸(如甘氨酸、组氨酸和精氨酸)和磷酸盐的高浓度稀释溶液在高温(约 80 °C)下干燥,可导致氨基酸:磷酸结晶盐的积累。随后将这些材料在 100 ℃ 下加热 1-3 天,可形成由多达 24 个单体单元组成的低聚甘氨酸,而精氨酸和组氨酸只能形成较短的低聚物(最多为三聚体)。总之,我们的研究结果表明,将磷酸链的催化作用与氨基酸:磷酸盐的结晶顺序相结合是一种可行的解决方案,可用于在弱酸性水热场情况下生成首批寡肽序列。此外,我们还建议结晶可以帮助克服环状低聚物的形成,这是众所周知的前生物聚合过程中阻碍链进一步增长的瓶颈。
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引用次数: 0
Activity-based metaproteomics driven discovery and enzymological characterization of potential α-galactosidases in the mouse gut microbiome 基于活性的元蛋白质组学发现小鼠肠道微生物组中潜在的α-半乳糖苷酶并对其进行酶学鉴定
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-16 DOI: 10.1038/s42004-024-01273-5
Jianbing Jiang, Diana Czuchry, Yanxia Ru, Huipai Peng, Junfeng Shen, Teng Wang, Wenjuan Zhao, Weihua Chen, Sen-Fang Sui, Yaowang Li, Nan Li
The gut microbiota offers an extensive resource of enzymes, but many remain uncharacterized. To distinguish the activities of similar annotated proteins and mine the potentially applicable ones in the microbiome, we applied an effective Activity-Based Metaproteomics (ABMP) strategy using a specific activity-based probe (ABP) to screen the entire gut microbiome for directly discovering active enzymes and their potential applications, not for exploring host-microbiome interactions. By using an activity-based cyclophellitol aziridine probe specific to α-galactosidases (AGAL), we successfully identified and characterized several gut microbiota enzymes possessing AGAL activities. Cryo-electron microscopy analysis of a newly characterized enzyme (AGLA5) revealed the covalent binding conformations between the AGAL5 active site and the cyclophellitol aziridine ABP, which could provide insights into the enzyme’s catalytic mechanism. The four newly characterized AGALs have diverse potential activities, including raffinose family oligosaccharides (RFOs) hydrolysis and enzymatic blood group transformation. Collectively, we present a ABMP platform that facilitates gut microbiota AGALs discovery, biochemical activity annotations and potential industrial or biopharmaceutical applications. The gut microbiota offers an extensive resource of enzymes, however, many remain uncharacterized. Here, the authors apply an activity-based metaproteomics strategy using an activity-based cyclophellitol aziridine probe specific to α-galactosidases (AGAL), and identify and characterize several gut microbiota enzymes possessing AGAL activities.
肠道微生物群提供了广泛的酶资源,但许多酶仍未定性。为了区分类似注释蛋白质的活性并挖掘微生物群中潜在的适用蛋白质,我们采用了一种有效的基于活性的元蛋白质组学(ABMP)策略,使用特定的基于活性的探针(ABP)筛选整个肠道微生物群,直接发现活性酶及其潜在应用,而不是探索宿主与微生物群之间的相互作用。通过使用特异于α-半乳糖苷酶(AGAL)的基于活性的环黄酮氮丙啶探针,我们成功鉴定并描述了几种具有AGAL活性的肠道微生物群酶。对一种新鉴定酶(AGLA5)的冷冻电镜分析揭示了AGAL5活性位点与环黄酮氮丙啶ABP之间的共价结合构象,这有助于深入了解该酶的催化机理。这四种新表征的 AGALs 具有多种潜在活性,包括棉子糖家族低聚糖(RFO)水解和酶促血型转化。总之,我们提出了一个 ABMP 平台,该平台有助于肠道微生物群 AGALs 的发现、生化活性注释以及潜在的工业或生物制药应用。肠道微生物群提供了大量的酶资源,但许多酶仍未定性。在本文中,作者采用了一种基于活性的元蛋白质组学策略,使用一种特异于α-半乳糖苷酶(AGAL)的基于活性的环黄酮氮丙啶探针,鉴定并描述了几种具有AGAL活性的肠道微生物群酶。
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引用次数: 0
Mechanistic insights into a heterobifunctional degrader-induced PTPN2/N1 complex 异功能降解器诱导 PTPN2/N1 复合物的机理探究
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-16 DOI: 10.1038/s42004-024-01263-7
Qi Hao, Manoj K. Rathinaswamy, Kelly L. Klinge, Matthew Bratkowski, Amirhossein Mafi, Christina K. Baumgartner, Keith M. Hamel, Gesine K. Veits, Rinku Jain, Claudio Catalano, Mark Fitzgerald, Alexander W. Hird, Eunice Park, Harit U. Vora, James A. Henderson, Kenton Longenecker, Charles W. Hutchins, Wei Qiu, Giovanna Scapin, Qi Sun, Vincent S. Stoll, Chaohong Sun, Ping Li, Dan Eaton, David Stokoe, Stewart L. Fisher, Christopher G. Nasveschuk, Marcia Paddock, Michael E. Kort
PTPN2 (protein tyrosine phosphatase non-receptor type 2, or TC-PTP) and PTPN1 are attractive immuno-oncology targets, with the deletion of Ptpn1 and Ptpn2 improving response to immunotherapy in disease models. Targeted protein degradation has emerged as a promising approach to drug challenging targets including phosphatases. We developed potent PTPN2/N1 dual heterobifunctional degraders (Cmpd-1 and Cmpd-2) which facilitate efficient complex assembly with E3 ubiquitin ligase CRL4CRBN, and mediate potent PTPN2/N1 degradation in cells and mice. To provide mechanistic insights into the cooperative complex formation introduced by degraders, we employed a combination of structural approaches. Our crystal structure reveals how PTPN2 is recognized by the tri-substituted thiophene moiety of the degrader. We further determined a high-resolution structure of DDB1-CRBN/Cmpd-1/PTPN2 using single-particle cryo-electron microscopy (cryo-EM). This structure reveals that the degrader induces proximity between CRBN and PTPN2, albeit the large conformational heterogeneity of this ternary complex. The molecular dynamic (MD)-simulations constructed based on the cryo-EM structure exhibited a large rigid body movement of PTPN2 and illustrated the dynamic interactions between PTPN2 and CRBN. Together, our study demonstrates the development of PTPN2/N1 heterobifunctional degraders with potential applications in cancer immunotherapy. Furthermore, the developed structural workflow could help to understand the dynamic nature of degrader-induced cooperative ternary complexes. PTPN2 (protein tyrosine phosphatase non-receptor type 2) and PTPN1 are attractive immuno-oncology targets, however, targeting PTPN2/N1 poses significant challenges. Here, the authors report the development of potent PTPN2/N1 heterobifunctional degraders and reveal biochemical and structural insights into the formation of ternary structures with cereblon E3 ligase by X-ray diffraction, cryo-EM and MD simulations.
PTPN2(蛋白酪氨酸磷酸酶非受体 2 型,或 TC-PTP)和 PTPN1 是极具吸引力的免疫肿瘤学靶点,在疾病模型中,Ptpn1 和 Ptpn2 的缺失可改善对免疫疗法的反应。靶向蛋白降解已成为包括磷酸酶在内的药物挑战靶点的一种有前途的方法。我们开发出了强效的 PTPN2/N1 双异构降解剂(Cmpd-1 和 Cmpd-2),它们能促进与 E3 泛素连接酶 CRL4CRBN 的高效复合物组装,并在细胞和小鼠体内介导强效的 PTPN2/N1 降解。为了从机理上深入了解降解器引入的合作复合物形成,我们采用了多种结构方法。我们的晶体结构揭示了 PTPN2 如何被降解剂的三取代噻吩分子识别。我们还利用单颗粒冷冻电镜(cryo-EM)测定了 DDB1-CRBN/Cmpd-1/PTPN2 的高分辨率结构。该结构揭示了降解器诱导了 CRBN 和 PTPN2 之间的接近,尽管该三元复合物具有很大的构象异质性。根据低温电子显微镜结构构建的分子动力学(MD)模拟显示了 PTPN2 的大量刚体运动,并说明了 PTPN2 和 CRBN 之间的动态相互作用。总之,我们的研究证明了 PTPN2/N1 异功能降解剂的开发具有在癌症免疫疗法中应用的潜力。此外,所开发的结构工作流程有助于理解降解剂诱导的合作三元复合物的动态性质。PTPN2(蛋白酪氨酸磷酸酶非受体2型)和PTPN1是极具吸引力的免疫肿瘤学靶标,然而靶向PTPN2/N1却面临着巨大的挑战。在此,作者报告了强效 PTPN2/N1 异功能降解剂的开发情况,并通过 X 射线衍射、低温电子显微镜和 MD 模拟揭示了与脑龙 E3 连接酶形成三元结构的生化和结构见解。
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引用次数: 0
Quantitative analysis of electroporation-mediated intracellular delivery via bioorthogonal luminescent reaction 通过生物正交发光反应对电穿孔介导的细胞内输送进行定量分析。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-15 DOI: 10.1038/s42004-024-01266-4
Shiqi Wang, Mariia V. Shcherbii, Sami-Pekka Hirvonen, Gudrun Silvennoinen, Mirkka Sarparanta, Hélder A. Santos
Efficient intracellular delivery is crucial for biotherapeutics, such as proteins, oligonucleotides, and CRISPR/Cas9 gene-editing systems, to achieve their efficacy. Despite the great efforts of developing new intracellular delivery carriers, the lack of straightforward methods for intracellular delivery quantification limits further development in this area. Herein, we designed a simple and versatile bioorthogonal luminescent reaction (BioLure assay) to analyze intracellular delivery. Our results suggest that BioLure can be used to estimate the amount of intracellularly delivered molecules after electroporation, and the estimation by BioLure is in good correlation with the results from complementary methods. Furthermore, we used BioLure assay to correlate the intracellularly-delivered RNase A amount with its tumoricidal activity. Overall, BioLure is a versatile tool for understanding the intracellular delivery process on live cells, and establishing the link between the cytosolic concentration of intracellularly-delivered biotherapeutics and their therapeutic efficacy. Efficient intracellular delivery is crucial for biotherapeutics to achieve their efficacy, however, evaluation of delivery efficiency remains challenging. Here, the authors design a bioorthogonal luminescent reaction to analyze intracellular delivery, showing the application in electroporation-mediated protein delivery.
高效的细胞内递送对于蛋白质、寡核苷酸和 CRISPR/Cas9 基因编辑系统等生物治疗药物发挥疗效至关重要。尽管人们在开发新的细胞内递送载体方面付出了巨大努力,但由于缺乏直接的细胞内递送定量方法,限制了这一领域的进一步发展。在此,我们设计了一种简单而通用的生物正交发光反应(BioLure 检测法)来分析细胞内递送。我们的研究结果表明,BioLure 可用于估算电穿孔后细胞内递送分子的数量,而且 BioLure 的估算结果与其他方法的结果有很好的相关性。此外,我们还利用 BioLure 分析法将细胞内递送的 RNase A 量与其杀瘤活性联系起来。总之,BioLure 是一种多功能工具,可用于了解活细胞的胞内递送过程,并建立胞内递送生物治疗药物的细胞膜浓度与其疗效之间的联系。
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引用次数: 0
Influence of the backbone chemistry and ionic functional groups of five pairs of oppositely charged polyelectrolytes on complex coacervation 五对带相反电荷的聚电解质的骨架化学和离子官能团对络合物凝聚的影响。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-15 DOI: 10.1038/s42004-024-01271-7
Yuri Hong, Surim Yoo, Jihoon Han, Junseong Kim, Yongjin Lee, YongSeok Jho, Youn Soo Kim, Dong Soo Hwang
Complex coacervation plays an important role in various fields. Here, the influences of the backbone chemistry and ionic functional groups of five pairs of oppositely charged polyelectrolytes on complex coacervation were investigated. These pairs include synthetic polymers with aliphatic hydrocarbon backbones, peptides with amide bonds, and carbohydrates with glycosidic linkages. Despite sharing identical charged groups, specific pairs displayed distinct liquid/liquid and liquid/solid phase separations depending on the polyelectrolyte mixing ratio, buffer, and ionic strength. The coacervate phase boundary broadened in the orders: glycosidic linkages > amide backbone > aliphatic hydrocarbon backbone, and Tris-phosphate > Tris-acetate > Tris-chloride buffers. Coacervates prepared from polyelectrolytes with lower solubilities in water resisted disassembly at high salt concentrations, and their merge rate was slow. These observations suggest that the hydrophobic segments in polyelectrolytes interfere with the formation of complex coacervates; however, following coacervate formation, the hydrophobic segments render the coacervates stable and elastic. Complex coacervation is propelled by the electrostatic association between oppositely charged polyelectrolytes, but the factors that drive complex coacervation have yet to be fully understood. Here, the authors investigate the influence of the backbone chemistry and ionic functional groups of five pairs of oppositely charged polyelectrolytes on complex coacervation.
络合物共保在多个领域发挥着重要作用。本文研究了五对带相反电荷的聚电解质的骨架化学和离子官能团对络合物凝聚的影响。这五对聚电解质包括具有脂肪烃骨架的合成聚合物、具有酰胺键的肽和具有糖苷键的碳水化合物。尽管共用相同的带电基团,但根据聚电解质混合比、缓冲液和离子强度的不同,特定配对显示出不同的液相/液相和液相/固相分离。共凝胶的相界按照糖苷键>酰胺骨架>脂肪烃骨架,以及磷酸三酯>醋酸三酯>氯化物三酯缓冲液的顺序扩大。用在水中溶解度较低的聚电解质制备的凝聚体在高浓度盐溶液中不易分解,而且其合并速度较慢。这些观察结果表明,聚电解质中的疏水片段会干扰复合凝聚态的形成;然而,凝聚态形成后,疏水片段会使凝聚态变得稳定而富有弹性。
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引用次数: 0
Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy 线粒体靶向光动力和光热疗法中的蓝染料。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-13 DOI: 10.1038/s42004-024-01256-6
Zdeněk Kejík, Jan Hajduch, Nikita Abramenko, Frédéric Vellieux, Kateřina Veselá, Jindřiška Leischner Fialová, Kateřina Petrláková, Kateřina Kučnirová, Robert Kaplánek, Ameneh Tatar, Markéta Skaličková, Michal Masařík, Petr Babula, Petr Dytrych, David Hoskovec, Pavel Martásek, Milan Jakubek
Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Here, the authors summarize the promise and limitations of cyanine dyes in enhancing mitochondrial PDT and PTT in cancer treatment.
线粒体失调在致癌过程中起着重要作用。另一方面,线粒体的不稳定性会严重抑制癌细胞的生存能力和转移潜力。光动力疗法和光热疗法(PDT 和 PTT)可有效靶向线粒体,提供创新的非侵入性抗癌治疗模式。具有线粒体强选择性的氰基染料在增强 PDT 和 PTT 方面显示出巨大的潜力。本文讨论了氰基染料在线粒体透射光治疗和线粒体穿刺治疗中的潜力和局限性,以及它们在联合疗法、治疗技术和最佳给药系统中的应用。此外,还介绍了使用光活性氰基染料进行声动力疗法的新方法,突显了癌症治疗的进展。
{"title":"Cyanine dyes in the mitochondria-targeting photodynamic and photothermal therapy","authors":"Zdeněk Kejík, Jan Hajduch, Nikita Abramenko, Frédéric Vellieux, Kateřina Veselá, Jindřiška Leischner Fialová, Kateřina Petrláková, Kateřina Kučnirová, Robert Kaplánek, Ameneh Tatar, Markéta Skaličková, Michal Masařík, Petr Babula, Petr Dytrych, David Hoskovec, Pavel Martásek, Milan Jakubek","doi":"10.1038/s42004-024-01256-6","DOIUrl":"10.1038/s42004-024-01256-6","url":null,"abstract":"Mitochondrial dysregulation plays a significant role in the carcinogenesis. On the other hand, its destabilization strongly represses the viability and metastatic potential of cancer cells. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Cyanine dyes, with strong mitochondrial selectivity, show significant potential in enhancing PDT and PTT. The potential and limitations of cyanine dyes for mitochondrial PDT and PTT are discussed, along with their applications in combination therapies, theranostic techniques, and optimal delivery systems. Additionally, novel approaches for sonodynamic therapy using photoactive cyanine dyes are presented, highlighting advances in cancer treatment. Photodynamic and photothermal therapies (PDT and PTT) target mitochondria effectively, providing innovative and non-invasive anticancer therapeutic modalities. Here, the authors summarize the promise and limitations of cyanine dyes in enhancing mitochondrial PDT and PTT in cancer treatment.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-39"},"PeriodicalIF":5.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Activity of botulinum neurotoxin X and its structure when shielded by a non-toxic non-hemagglutinin protein 肉毒杆菌神经毒素 X 的活性及其在无毒非凝集素蛋白保护下的结构
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-13 DOI: 10.1038/s42004-024-01262-8
Markel Martínez-Carranza, Jana Škerlová, Pyung-Gang Lee, Jie Zhang, Ajda Krč, Abhishek Sirohiwal, Dave Burgin, Mark Elliott, Jules Philippe, Sarah Donald, Fraser Hornby, Linda Henriksson, Geoffrey Masuyer, Ville R. I. Kaila, Matthew Beard, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are the most potent toxins known and are used to treat an increasing number of medical disorders. All BoNTs are naturally co-expressed with a protective partner protein (NTNH) with which they form a 300 kDa complex, to resist acidic and proteolytic attack from the digestive tract. We have previously identified a new botulinum neurotoxin serotype, BoNT/X, that has unique and therapeutically attractive properties. We present the cryo-EM structure of the BoNT/X-NTNH/X complex and the crystal structure of the isolated NTNH protein. Unexpectedly, the BoNT/X complex is stable and protease-resistant at both neutral and acidic pH and disassembles only in alkaline conditions. Using the stabilizing effect of NTNH, we isolated BoNT/X and showed that it has very low potency both in vitro and in vivo. Given the high catalytic activity and translocation efficacy of BoNT/X, low activity of the full toxin is likely due to the receptor-binding domain, which presents very weak ganglioside binding and exposed hydrophobic surfaces. Botulinum neurotoxins (BoNTs) are a family of protein toxins produced by clostridial bacteria that cause muscle paralysis, and exhibit structural and functional diversity within the BoNTs family. Here, the authors report the cryo-EM structure complex of a newly identified serotype BoNT/X with their partner protein NTNH/X and reveal the complex’s pH-dependent stability and receptor-binding properties.
肉毒杆菌神经毒素(BoNTs)是已知毒性最强的毒素,被用于治疗越来越多的疾病。所有 BoNTs 都与一种保护性伙伴蛋白(NTNH)天然共表达,并与之形成 300 kDa 的复合物,以抵御来自消化道的酸性和蛋白水解攻击。我们之前发现了一种新的肉毒杆菌神经毒素血清型--BoNT/X,它具有独特的治疗特性。我们展示了 BoNT/X-NTNH/X 复合物的冷冻电镜结构和分离出的 NTNH 蛋白的晶体结构。出乎意料的是,BoNT/X 复合物在中性和酸性 pH 值下都很稳定,并且抗蛋白酶,只有在碱性条件下才会分解。利用 NTNH 的稳定作用,我们分离出了 BoNT/X,并证明它在体外和体内的效力都很低。鉴于 BoNT/X 具有很高的催化活性和转运功效,全毒素的低活性很可能是受体结合结构域造成的,该结构域具有很弱的神经节苷脂结合力和暴露的疏水表面。肉毒杆菌神经毒素(BoNTs)是由梭状芽孢杆菌产生的一系列蛋白质毒素,可导致肌肉麻痹,在 BoNTs 家族中表现出结构和功能的多样性。作者在本文中报告了新发现的血清型 BoNT/X 与其伙伴蛋白 NTNH/X 的低温电子显微镜结构复合物,并揭示了该复合物随 pH 值变化的稳定性和受体结合特性。
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引用次数: 0
Electrodeposition of porous metal-organic frameworks for efficient charge storage 用于高效电荷存储的多孔金属有机框架的电沉积。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-10 DOI: 10.1038/s42004-024-01260-w
Deepa B. Bailmare, Boris V. Malozyomov, Abhay D. Deshmukh
Efficient charge storage is a key requirement for a range of applications, including energy storage devices and catalysis. Metal-organic frameworks are potential materials for efficient charge storage due to their self-supported three-dimensional design. MOFs are high surface area materials made up of coordination of appropriate amounts of metal ions and organic linkers, hence used in various applications. Yet, creating an effective MOF nanostructure with reduced random crystal formation continues to be a difficult task. The energy efficiency and electrochemical yield of bulk electrodes are improved in this study by demonstrating an effective technique for growing MOFs over a conducting substrate utilizing electrodeposition. An exceptionally stable asymmetric supercapacitor is created when activated carbon cloth is combined with the resulting MOF structure that was directly synthesized via an electrochemical method resulting in 97% stability over 5k cycles which is higher than conventional processes. High performance in supercapacitors is ensured by this practical approach for producing MOF electrodes, making it a suitable structure for effective charge storage. Metal-organic frameworks (MOFs) are promising charge storage materials due to their high surface area, tunable pore size, and chemical diversity, but reliable and easy syntheses of MOF conductors are needed. Here, the authors report the electrodeposition synthesis of highly conductive cobalt MOF films and their application in a supercapacitor with a power density of 480 Wkg-1 and 5k cycle stability.
高效电荷存储是包括储能设备和催化等一系列应用的关键要求。金属有机框架具有自支撑三维设计,是高效电荷存储的潜在材料。MOF 是由适量金属离子和有机连接体配位而成的高比表面积材料,因此被广泛应用于各种领域。然而,创造一种有效的 MOF 纳米结构并减少随机晶体的形成仍然是一项艰巨的任务。本研究展示了一种利用电沉积在导电基底上生长 MOF 的有效技术,从而提高了块状电极的能效和电化学产率。当活性碳布与通过电化学方法直接合成的 MOF 结构结合在一起时,一种异常稳定的非对称超级电容器就诞生了,这种电容器在 5 千次循环中的稳定性高达 97%,高于传统工艺。这种生产 MOF 电极的实用方法确保了超级电容器的高性能,使其成为有效存储电荷的合适结构。
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引用次数: 0
Photodetachment photoelectron spectroscopy shows isomer-specific proton-coupled electron transfer reactions in phenolic nitrate complexes 光脱附光电子能谱显示了酚类硝酸盐复合物中的同分异构质子耦合电子转移反应。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-09 DOI: 10.1038/s42004-024-01257-5
Qinqin Yuan, Ziheng Zhang, Xiangtao Kong, Zicheng Ling, Hanhui Zhang, Longjiu Cheng, Xue-Bin Wang
The oxidation of phenolic compounds is one of the most important reactions prevalent in various biological processes, often explicitly coupled with proton transfers (PTs). Quantitative descriptions and molecular-level understanding of these proton-coupled electron transfer (PCET) reactions have been challenging. This work reports a direct observation of PCET in photodetachment (PD) photoelectron spectroscopy (PES) of hydrogen-bonded phenolic (ArOH) nitrate (NO3−) complexes, in which a much slower rising edge provides a spectroscopic signature to evidence PCET. Electronic structure calculations unveil the PCET processes to be isomer-specific, occurred only in those with their HOMOs localized on ArOH, leading to charge-separated transient states ArOH•+·NO3− triggered by ionizing phenols while simultaneously promoting PT from ArOH•+ to NO3−. Importantly, this study showcases that gas-phase PD-PES is a generic means enabling to identify PCET reactions with explicit structural and binding information. The oxidation of phenolic compounds is one of the most important reactions prevalent in various biological processes, but quantitative descriptions and molecular-level understanding of these proton-coupled electron transfer (PCET) reactions have been challenging. Here, the authors use photodetachment photoelectron spectroscopy to directly observe PCET in hydrogen-bonded phenolic nitrate complexes, in which a much slower rising edge provides a spectroscopic signature to evidence PCET
酚类化合物的氧化是各种生物过程中普遍存在的最重要反应之一,通常与质子转移(PTs)明确耦合。对这些质子耦合电子转移(PCET)反应的定量描述和分子水平的理解一直具有挑战性。这项研究报告了在氢键酚(ArOH)硝酸酯(NO3-)复合物的光脱离(PD)光电子能谱(PES)中直接观察到的 PCET,其中更慢的上升沿提供了证明 PCET 的光谱特征。电子结构计算揭示了 PCET 过程具有异构体特异性,只发生在 HOMO 定位于 ArOH 的异构体中,导致电离酚引发的电荷分离瞬态 ArOH-+-NO3-,同时促进从 ArOH-+ 到 NO3- 的 PT。重要的是,这项研究表明气相 PD-PES 是一种通用的方法,可以利用明确的结构和结合信息识别 PCET 反应。
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引用次数: 0
Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors 三唑类抑制剂对人类 p97/VCP ATPase 及其疾病突变体的异位抑制机制。
IF 5.9 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Pub Date : 2024-08-09 DOI: 10.1038/s42004-024-01267-3
Purbasha Nandi, Kira DeVore, Feng Wang, Shan Li, Joel D. Walker, Thanh Tung Truong, Matthew G. LaPorte, Peter Wipf, Heidi Schlager, John McCleerey, William Paquette, Rod Carlo A. Columbres, Taiping Gan, Yu-Ping Poh, Petra Fromme, Andrew J. Flint, Mark Wolf, Donna M. Huryn, Tsui-Fen Chou, Po-Lin Chiu
Human p97 ATPase is crucial in various cellular processes, making it a target for inhibitors to treat cancers, neurological, and infectious diseases. Triazole allosteric p97 inhibitors have been demonstrated to match the efficacy of CB-5083, an ATP-competitive inhibitor, in cellular models. However, the mechanism is not well understood. This study systematically investigates the structures of new triazole inhibitors bound to  both wild-type and disease mutant forms of p97 and measures their effects on function. These inhibitors bind at the interface of the D1 and D2 domains of each p97 subunit, shifting surrounding helices and altering the loop structures near the C-terminal α2 G helix to modulate domain-domain communications. A key structural moiety of the inhibitor affects the rotameric conformations of interacting side chains, indirectly modulating the N-terminal domain conformation in p97 R155H mutant. The differential effects of inhibitor binding to wild-type and mutant p97 provide insights into drug design with enhanced specificity, particularly for oncology applications. Human p97 ATPase, a critical drug target for neurodegenerative disorders and cancers, can be allosterically inhibited by triazole-based inhibitors. In this study, the authors investigate the structure and functions of newly designed triazole inhibitors in both wild-type and disease mutant forms of p97 to elucidate the previously unexplored inhibitory mechanisms, shedding new light on the design concept for p97 allosteric inhibitors.
人类 p97 ATPase 在各种细胞过程中起着关键作用,因此成为治疗癌症、神经疾病和传染性疾病抑制剂的靶点。在细胞模型中,三唑异构 p97 抑制剂已被证明与 ATP 竞争性抑制剂 CB-5083 的疗效相当。然而,人们对其机制还不甚了解。本研究系统地研究了与野生型和疾病突变型 p97 结合的新型三唑抑制剂的结构,并测量了它们对功能的影响。这些抑制剂结合在每个 p97 亚基的 D1 和 D2 结构域的界面上,移动周围的螺旋并改变 C 端 α2 G 螺旋附近的环结构,从而调节结构域与结构域之间的通讯。抑制剂的一个关键结构分子会影响相互作用侧链的旋转构象,从而间接调节 p97 R155H 突变体的 N 端结构域构象。抑制剂与野生型和突变型 p97 结合的不同效应为设计具有更强特异性的药物(尤其是肿瘤应用药物)提供了启示。
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Communications Chemistry
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