ChemBioChem最新文献_第10页

Amyloid Fibril Formation on Neuronal Cells in the Coexistence of Aβ40 and Aβ42. Aβ40和Aβ42共存时神经元细胞上淀粉样纤维的形成

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-25 DOI: 10.1002/cbic.202400603

Mayu Kawaguchi, Kenichi Kawano, Aoi Taniguchi, Atsushi Tanaka, Katsumi Matsuzaki

{"title":"Amyloid Fibril Formation on Neuronal Cells in the Coexistence of Aβ40 and Aβ42.","authors":"Mayu Kawaguchi, Kenichi Kawano, Aoi Taniguchi, Atsushi Tanaka, Katsumi Matsuzaki","doi":"10.1002/cbic.202400603","DOIUrl":"10.1002/cbic.202400603","url":null,"abstract":"The abnormal aggregation and subsequent deposition of amyloid β-protein (Aβ) in the brain are considered central to the pathogenesis of Alzheimer's disease. The two major species of Aβ are Aβ40 and Aβ42, present at an approximate ratio of 9 : 1. Accumulating evidence suggests that neuronal membranes are an important platform of amyloidogenesis by Aβ. However, information on the aggregational behaviors of coexistent Aβ40 and Aβ42 on membranes is lacking. In this study, the aggregation and resultant cytotoxicity of coexistent Aβ40 and Aβ42 at a physiologically relevant ratio were investigated by fluorescence techniques. We found that the degree of coexistence of both Aβs in aggregates increased as the assembly proceeded, and reached a maximum in fibrils. Cross-seeding experiments supported the hypothesis that Aβ40 and Aβ42 interact with each other in the fibrillar states when formed on membranes. However, the cytotoxicity of the mixed fibrils was weaker than that of Aβ42 fibrils, suggesting the possibility that Aβ40 attenuates the toxicity of Aβ42 by forming mixed fibrils. In contrast, the degree of coexistence was significantly lower in aqueous phase aggregation, highlighting different aggregation mechanisms between in membranes and in the aqueous phase.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337757","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

Mechanisms in the Synthesis of S-Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study. 使用马肝醇脱氢酶与 1,4-NADH 生物模拟辅助因子 N-苄基-1,4-二氢烟酰胺合成 S-醇的机制：混合计算研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-25 DOI: 10.1002/cbic.202400727

Matteo Farina, Matteo Capone, Enrico Bodo, Richard H Fish, Massiliano Aschi, Alessandro Marrone, Isabella Daidone

{"title":"Mechanisms in the Synthesis of S-Alcohols with 1,4-NADH Biomimetic Co-factor N-Benzyl-1,4-dihydronicotinamide using Horse Liver Alcohol Dehydrogenase: A Hybrid Computational Study.","authors":"Matteo Farina, Matteo Capone, Enrico Bodo, Richard H Fish, Massiliano Aschi, Alessandro Marrone, Isabella Daidone","doi":"10.1002/cbic.202400727","DOIUrl":"10.1002/cbic.202400727","url":null,"abstract":"The enantioselective reduction of prochiral ketones catalyzed by horse liver alcohol dehydrogenase (HLADH), was investigated via a hybrid computational approach, for molecular reactions involved in chiral synthesis of S-alcohols, when the natural co-factor, 1,4-dihyronicotinamide adenine dinucleotide, 1,4-NADH, was replaced with biomimetic co-factor, N-benzyl-1,4-dihydronicotinamide, 1. We surmised that different hydride and proton transfer mechanisms were involved using co-factor, 1. An alternative mechanism, where the hydride transfer step occurred, via an η1-keto-S-η2-5,6-1,4-dihydronicotinamide-Zn(II) complex, was previously investigated with a model of the HLADH-Zn(II) catalytic site (J. Organometal. Chem. 2021, 943, 121810). Presently, we studied canonical and alternative mechanisms compared to models of the entire enzyme structure. We disproved the η2-Zn(II) complex, and discovered a canonical hydride transfer from biomimetic 1,4-NADH, 1, to the Zn(II) bound prochiral ketone substrate, followed by a new proton relay, consisting of a water chain connecting His51 to Ser48 that accomplished the S-alkoxy anion's protonation to yield the final S-alcohol product. The HLADH catalysis, with biomimetic co-factor, 1, that replaced the ribose group, the 5'-diphosphate groups, and the adenine nucleotide with a N-benzyl group, has provided a new paradigm for the design of other structures of 1,4-NADH biomimetic co-factors, including their economic value in biocatalysis reactions.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337760","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

Biosensor-Guided Engineering of a Baeyer-Villiger Monooxygenase for Aliphatic Ester Production 生物传感器引导的用于脂肪族酯生产的拜尔-维利格单加氧酶工程设计

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-25 DOI: 10.1002/cbic.202400712

Thaleia Sakoleva, Florian Vesenmaier, Lena Koch, Jarne E. Schunke, Kay D. Novak, Sascha Grobe, Mark Dörr, Uwe T. Bornscheuer, Thomas Bayer

{"title":"Biosensor-Guided Engineering of a Baeyer-Villiger Monooxygenase for Aliphatic Ester Production","authors":"Thaleia Sakoleva, Florian Vesenmaier, Lena Koch, Jarne E. Schunke, Kay D. Novak, Sascha Grobe, Mark Dörr, Uwe T. Bornscheuer, Thomas Bayer","doi":"10.1002/cbic.202400712","DOIUrl":"https://doi.org/10.1002/cbic.202400712","url":null,"abstract":"Esters are valuable aroma compounds and can be produced enzymatically by Baeyer-Villiger monooxygenases (BVMOs) from (aliphatic) ketone precursors. However, a genetically encoded biosensor system for the assessment of BVMO activity and the detection of reaction products is missing. In this work, we assembled a synthetic enzyme cascade – featuring an esterase, an alcohol dehydrogenase, and LuxAB – in the heterologous host Escherichia coli. Target esters are produced by a BVMO, subsequently cleaved, and the corresponding alcohol oxidized through the artificial pathway. Ultimately, aldehyde products are detected in vivo by LuxAB, a luciferase from Photorhabdus luminescens that emits bioluminescence upon the oxidation of aldehydes to the corresponding carboxylates. This biosensor system greatly accelerated the screening and selection of active BVMO variants from a focused library, omitting commonly used low-throughput chromatographic analysis. Engineered enzymes accepted linear aliphatic ketones such as 2-undecanone and 2-dodecanone and exhibited improved ester formation.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317796","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

Molecular Networking-Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single-Molecule Stretching Assays. 以分子网络为指导，从田桥链霉菌（Streptomyces tanashiensis DSM 731）中发现一种新的抗肿瘤萘醌：单分子拉伸试验的启示。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-25 DOI: 10.1002/cbic.202400732

Teng Cai, Nanjin Ding, Yulong He, Tao Han, Yanyan Wang, Chengxin Liu, Qiqi He, Chen Liu, Aiying Li, Peng Zhang, Xiaofeng Cai

{"title":"Molecular Networking-Guided Discovery of a New Antitumor Pyranonaphthoquinone from Streptomyces tanashiensis DSM 731: Insights from Single-Molecule Stretching Assays.","authors":"Teng Cai, Nanjin Ding, Yulong He, Tao Han, Yanyan Wang, Chengxin Liu, Qiqi He, Chen Liu, Aiying Li, Peng Zhang, Xiaofeng Cai","doi":"10.1002/cbic.202400732","DOIUrl":"10.1002/cbic.202400732","url":null,"abstract":"Guided by molecular networking based on single-molecule stretching assay, an unprecedented pyranonaphthoquinone, methyl kalafunginate (1) and five known compounds 2-6 were isolated from Streptomyces tanashiensis DSM 731. Compound 1 was characterized through a combination of spectroscopic techniques, including 1D and 2D NMR analysis, ECD calculation, and X-ray crystallography. Interestingly, we discovered that compound 1 was spontaneously converted from kalafungin (4) in methanol solution. All isolated compounds, except for compound 3, were assessed for their cytotoxic potential against a panel of five human cancer cell lines: A549, HepG2, BxPC-3, SW620, and C4-2B. Compounds 1, 2, 4, and 5 exhibited remarkable cytotoxicity with IC50 values below 2.382 μM, suggesting their potential as promising anticancer agents. These findings highlight the significance of using a combined approach of single-molecule stretching assays and molecular networking for efficiently discovering novel natural products with potential therapeutic applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337761","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

Cavity-Based Discovery of New Fatty Acid Photodecarboxylases. 基于空腔的新型脂肪酸光脱羧酶的发现。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400631

Stefan Simić, Marco Cespugli, Michael C Hetmann, Ursula Kahler, Valentina Jurkaš, Marikagiusy Di Giacomo, Maria E Russo, Antonio Marzocchella, Christian C Gruber, Bettina M Nestl, Christoph K Winkler, Wolfgang Kroutil

{"title":"Cavity-Based Discovery of New Fatty Acid Photodecarboxylases.","authors":"Stefan Simić, Marco Cespugli, Michael C Hetmann, Ursula Kahler, Valentina Jurkaš, Marikagiusy Di Giacomo, Maria E Russo, Antonio Marzocchella, Christian C Gruber, Bettina M Nestl, Christoph K Winkler, Wolfgang Kroutil","doi":"10.1002/cbic.202400631","DOIUrl":"10.1002/cbic.202400631","url":null,"abstract":"Light-dependent fatty acid photodecarboxylases (FAPs) hold significant potential for biotechnology, due to their capability to produce alka(e)nes directly from the corresponding (un)saturated natural fatty acids requiring light as the only reagent. This study expands the family of FAPs through cavity-based enzyme discovery methods. Thirty enzyme candidates with potential photodecarboxylation activity were identified by matching the cavities of four related template structures against the Protein Data Bank's flavoproteins, a library of proteins identified via the Foldseek Search Server, and homology models of sequences resulting from BLAST. Subsequent docking experiments narrowed this library to ten promising enzymes, which were expressed and assessed in vitro, identifying four photodecarboxylases. Out of these enzymes, the GMC oxidoreductase from Coccomyxa sp. Obi (CoFAP) was characterized in detail, which revealed high activity in the decarboxylation reactions of palmitic acid and octanoic acid and a broad pH tolerance (pH 6.5-9.5).","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306688","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

Photoactivable CRISPR for Biosensing and Cancer Therapy. 用于生物传感和癌症治疗的光活性 CRISPR。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400685

Siyuan Wang, Jiaqi Wang, Baijiang Li, Jingjing Zhang

引用次数: 0

Substrate-Multiplexed Assessment of Aromatic Prenyltransferase Activity. 芳香族戊烯基转移酶活性的底物多复性评估

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400680

Peyton M Higgins, Nicolette G Wehrli, Andrew R Buller

引用次数: 0

Optogenetic Tools for Regulating RNA Metabolism and Functions. 调节 RNA 代谢和功能的光遗传学工具。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-24 DOI: 10.1002/cbic.202400615

Ru Zheng, Zhaolin Xue, Mingxu You

引用次数: 0

Chemical Tools for Probing the Ub/Ubl Conjugation Cascades. 探测 Ub/Ubl 共轭级联的化学工具。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-23 DOI: 10.1002/cbic.202400659

Tomasz Kochańczyk, Michael Fishman, Christopher D Lima

{"title":"Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.","authors":"Tomasz Kochańczyk, Michael Fishman, Christopher D Lima","doi":"10.1002/cbic.202400659","DOIUrl":"10.1002/cbic.202400659","url":null,"abstract":"Conjugation of ubiquitin (Ub) and structurally related ubiquitin-like proteins (Ubls), essential for many cellular processes, employs multi-step reactions orchestrated by specific E1, E2 and E3 enzymes. The E1 enzyme activates the Ub/Ubl C-terminus in an ATP-dependent process that results in the formation of a thioester linkage with the E1 active site cysteine. The thioester-activated Ub/Ubl is transferred to the active site of an E2 enzyme which then interacts with an E3 enzyme to promote conjugation to the target substrate. The E1-E2-E3 enzymatic cascades utilize labile intermediates, extensive conformational changes, and vast combinatorial diversity of short-lived protein-protein complexes to conjugate Ub/Ubl to various substrates in a regulated manner. In this review, we discuss various chemical tools and methods used to study the consecutive steps of Ub/Ubl activation and conjugation, which are often too elusive for direct studies. We focus on methods developed to probe enzymatic activities and capture and characterize stable mimics of the transient intermediates and transition states, thereby providing insights into fundamental mechanisms in the Ub/Ubl conjugation pathways.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306689","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

Amyloid-like Aggregation Propensities of Metabolites- Homogentisic Acid, N-Acetyl Aspartic Acid and Isovaleric Acid. 代谢物--高戊二酸、N-乙酰天冬氨酸和异戊二酸的淀粉样凝集倾向。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-23 DOI: 10.1002/cbic.202400109

Raj Dave, Ankita Jaiswal, Anam Naseer, Ankita Tripathi, Monisha Patel, Neeraja Revi, Aravind Kumar Rengan, Kshatresh Dutta Dubey, Aamir Nazir, Sandeep Verma, Nidhi Gour

{"title":"Amyloid-like Aggregation Propensities of Metabolites- Homogentisic Acid, N-Acetyl Aspartic Acid and Isovaleric Acid.","authors":"Raj Dave, Ankita Jaiswal, Anam Naseer, Ankita Tripathi, Monisha Patel, Neeraja Revi, Aravind Kumar Rengan, Kshatresh Dutta Dubey, Aamir Nazir, Sandeep Verma, Nidhi Gour","doi":"10.1002/cbic.202400109","DOIUrl":"10.1002/cbic.202400109","url":null,"abstract":"The transformation of metabolites into amyloidogenic aggregates represent an intriguing dimension in the pathophysiology of metabolic disorders, including alkaptonuria, canavan disease, and isovaleric acidemia. Central to this phenomenon are the metabolites homogentisic acid (HA), N-acetyl aspartic acid (NAA), and isovaleric acid (IVA), which we found, weave an intricate network of self-assembled structures. Leveraging an array of microscopy techniques, we traced the morphological behavior of these assemblies that exhibit concentration and time-dependent morphological transitions from isolated globules to clustered aggregates. MD simulation studies suggest significant role of hydrogen bonding interactions in the aggregation process. While displaying strong amyloidogenic propensity in solution, these aged aggregates were significantly cytotoxic to mouse neural N2a cell lines. In vivo effect in Caenorhabditis elegans (C. elegans) nematode further validated cytotoxicity of aggregates. Our findings provide fresh insights to amyloidogenic nature of HA, NAA, and IVA aggregates and their possible role in associated metabolic disorders such as alkaptonuria, canavan disease and isovaleric acidemia.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306687","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