ChemBioChem最新文献_第2页

DNA-Encoded Noncanonical Substrate Library for Protease Profiling 用于蛋白酶分析的 DNA编码非调控底物库

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-19 DOI: 10.1002/cbic.202400559

Huiya Zhang, Yuyu Xing, Yixuan Yang, Bixi Tang, Zhaoyun Zong, Jia Li, Yi Zang, Matthew Bogyo, Xiaojie Lu, Shiyu Chen

{"title":"DNA-Encoded Noncanonical Substrate Library for Protease Profiling","authors":"Huiya Zhang, Yuyu Xing, Yixuan Yang, Bixi Tang, Zhaoyun Zong, Jia Li, Yi Zang, Matthew Bogyo, Xiaojie Lu, Shiyu Chen","doi":"10.1002/cbic.202400559","DOIUrl":"https://doi.org/10.1002/cbic.202400559","url":null,"abstract":"Profiling the substrate sequence preferences of proteases is important for understanding both biological functions as well as for designing protease inhibitors. Several methods are available for profiling the sequence specificity of proteases. However, there is currently no rapid and high-throughput method to profile specificity of proteases for noncanonical substrates. In this study, we described a strategy to use a DNA-encoded noncanonical substrate library to identify the protease substrates composed of both canonical and noncanonical amino acids. This approach uses a DNA-encoded peptide library and introduces a biotin molecule at the N-terminus to immobilize the library on a solid support. Upon protease hydrolysis, the released DNA tag of the substrate peptides can be sequenced to identify the substrate structures. Using this approach, we profiled trypsin and fibroblast activation protein α and discovered noncanonical substrates that were more efficiently cleaved than the commonly used substrates. The identified substrates of FAP were further used to design corresponding covalent inhibitors containing non-canonical sequences with high potency for the target protease. Overall, our approach can aid in the development of new protease substrates and inhibitors.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256859","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

Untangling the complexity and impact of tau protein ubiquitination 解开 tau 蛋白泛素化的复杂性及其影响

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-18 DOI: 10.1002/cbic.202400566

Daniele Trivellato, Francesca Munari, Michael Assfalg, Stefano Capaldi, Mariapina D'Onofrio

{"title":"Untangling the complexity and impact of tau protein ubiquitination","authors":"Daniele Trivellato, Francesca Munari, Michael Assfalg, Stefano Capaldi, Mariapina D'Onofrio","doi":"10.1002/cbic.202400566","DOIUrl":"https://doi.org/10.1002/cbic.202400566","url":null,"abstract":"The microtubule-associated protein tau is an intrinsically disordered protein highly expressed in neuronal axons. In healthy neurons, tau regulates microtubule dynamics and neurite outgrowth. However, pathological conditions can trigger aberrant tau aggregation into insoluble filaments, a hallmark of neurodegenerative disorders known as tauopathies. Tau undergoes diverse posttranslational modifications (PTMs), suggesting complex regulation and potentially varied functions. Among PTMs, the role and mechanisms of ubiquitination in physiology and disease have remained enigmatic. The past three decades have witnessed the emergence of key studies on tau protein ubiquitination. In this concept, we discuss how these investigations have begun to shed light on the ubiquitination patterns of physiological and pathological tau, the responsible enzymatic machinery, and the influence of ubiquitination on tau aggregation. We also provide an overview of the semi-synthetic methods that have enabled in vitro investigations of conformational transitions of tau induced by ubiquitin modification. Finally, we discuss future perspectives in the field necessary to elucidate the molecular mechanisms of tau ubiquitination and clearance.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256860","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

A High‐Throughput Visual Screen for the Directed Evolution of C β ‐stereoselectivity of L‐threonine Aldolase 定向进化 L-苏氨酸醛醇酶 C β-立体选择性的高通量视觉筛选

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-18 DOI: 10.1002/cbic.202400637

You-Xue Zhao, Hai-Peng Li, Li-Hang Cheng, Chun-Xiu Li, Jiang Pan, Jian-He Xu

引用次数: 0

Understanding Cytochrome P450 Enzyme Substrate Inhibition and Prospects for Elimination Strategies 了解细胞色素 P450 酶的底物抑制作用和消除策略的前景

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-17 DOI: 10.1002/cbic.202400297

Yisang Zhang, Guobin Zhang, Taichang Wang, Yu Chen, Junqing Wang, Piwu Li, Ruiming Wang, Jing Su

{"title":"Understanding Cytochrome P450 Enzyme Substrate Inhibition and Prospects for Elimination Strategies","authors":"Yisang Zhang, Guobin Zhang, Taichang Wang, Yu Chen, Junqing Wang, Piwu Li, Ruiming Wang, Jing Su","doi":"10.1002/cbic.202400297","DOIUrl":"https://doi.org/10.1002/cbic.202400297","url":null,"abstract":"Cytochrome P450 (CYP450) enzymes, which are widely distributed and pivotal in various biochemical reactions, catalyze diverse processes such as hydroxylation, epoxidation, dehydrogenation, dealkylation, nitrification, and bond formation. These enzymes have been applied in drug metabolism, antibiotic production, bioremediation, and fine chemical synthesis. Recent research revealed that CYP450 catalytic kinetics deviated from the classic Michaelis–Menten model. A notable substrate inhibition phenomenon that affects the catalytic efficiency of CYP450 at high substrate concentrations was identified. However, the substrate inhibition of various reactions catalyzed by CYP450 enzymes have not been comprehensively reviewed. This review describes CYP450 substrate inhibition examples and atypical Michaelis–Menten kinetic models, and provides insight into mechanisms of these enzymes. We also reviewed 3D structure and dynamics of CYP450 with substrate binding. Outline methods for alleviating substrate inhibition in CYP450 and other enzymes, including traditional fermentation approaches and protein engineering modifications. The comprehensive analysis presented in this study lays the foundation for enhancing the catalytic efficiency of CYP450 by deregulating substrate inhibition.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256889","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

Cyclometalated Iridium(III) Complex with Substituted Benzimidazole: pH Directed Organelle‐specific Localization within Lysosome 环甲基铱(III)与取代的苯并咪唑配合物：溶酶体内 pH 值定向的细胞器特异性定位

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-17 DOI: 10.1002/cbic.202400597

Subhra Sil, Afaq Hussain, Jayasri Das Sarma, Parna Gupta

引用次数: 0

Cover Feature: Synthesis and Thermodynamic Evaluation of Sialyl-Tn MUC1 Glycopeptides Binding to Macrophage Galactose-Type Lectin (ChemBioChem 18/2024) 封面专题：与巨噬细胞半乳糖型凝集素结合的 Sialyl-Tn MUC1 糖肽的合成与热力学评估（ChemBioChem 18/2024）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-16 DOI: 10.1002/cbic.202481804

Ramya Ayyalasomayajula, Ivet Boneva, David Ormaza, Andrew Whyte Jr., Kamran Farook, Zachary Gorlin, Evelyn Yancey, Sabine André, Herbert Kaltner, Maré Cudic

引用次数: 0

Front Cover: Probing Glycerolipid Metabolism using a Caged Clickable Glycerol-3-Phosphate Probe (ChemBioChem 18/2024) 封面：使用笼式可点击甘油-3-磷酸酯探针探测甘油酯代谢（ChemBioChem 18/2024）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-09-16 DOI: 10.1002/cbic.202481801

Dr. Jinchao Lou, Dr. Christelle F. Ancajas, Dr. Yue Zhou, Nicolas S. Lane, Prof. Dr. Todd B. Reynolds, Prof. Michael D. Best

引用次数: 0

A Thermostable Heme Protein Fold Adapted for Stereoselective C‐H Bond Hydroxylation Using Peroxygenase Activity 利用过氧化氢酶活性进行立体选择性 C-H 键羟基化的恒温血红素蛋白折叠结构

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-14 DOI: 10.1002/cbic.202400737

Tuhin Das, Eva F. Hayball, Alix C. Harlington, Stephen Graham Bell

{"title":"A Thermostable Heme Protein Fold Adapted for Stereoselective C‐H Bond Hydroxylation Using Peroxygenase Activity","authors":"Tuhin Das, Eva F. Hayball, Alix C. Harlington, Stephen Graham Bell","doi":"10.1002/cbic.202400737","DOIUrl":"https://doi.org/10.1002/cbic.202400737","url":null,"abstract":"Thermostable protein folds of natural and synthetic origin are highly sought‐after templates for biocatalyst generation due to their enhanced stability to elevated temperatures which overcomes one of the major limitations of applying enzymes for synthesis. Cytochrome P450 enzymes (CYPs) are a family of heme‐thiolate monooxygenases that catalyse the oxidation of their substrates in a highly stereo‐ and regio‐selective manner. The CYP enzyme (CYP107PQ1) from the thermophilic bacterium Meiothermus ruber binds the norisoprenoid β‐ionone and was employed as a scaffold for catalyst design. The I‐helix was modified to convert this enzyme from a monooxygenase into a peroxygenase (CYP107PQ1QE), enabling the enantioselective oxidation of β‐ionone to (S)‐4‐hydroxy‐β‐ionone (94% e.e.). The enzyme was resistant to 20 mM H2O2, 20% (v/v) of organic solvent, supported over 1700 turnovers and was fully functional after incubation at 60 °C for 1 h and 30 °C for 365 days. The reaction was scaled‐up to generate multi milligram quantities of the product for characterisation. Overall, we demonstrate that sourcing a CYP protein fold from an extremophile enabled the design of a highly stable enzyme for stereoselective C‐H bond activation only using H2O2 as the oxidant, providing a viable strategy for future biocatalyst design.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256891","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

Synthesis of a 13C/2H Labeled Building Block to Probe the Phosphotyrosine Interactome Using Biomolecular NMR Spectroscopy. 合成 13C/2H 标记构件，利用生物分子核磁共振波谱探测磷酪氨酸相互作用组。

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-14 DOI: 10.1002/cbic.202400663

Sarah Kratzwald, Roman Lichtenecker, Thomas C. Schwarz, Karin Ledolter, Matus Hlavac, Manuel Felkl, Christian F.W. Becker, Robert Konrat

引用次数: 0

The Multifunctional Preprotein Binding Domain of SecA SecA 的多功能前蛋白结合域

IF 3.2 4区生物学

ChemBioChem Pub Date : 2024-09-13 DOI: 10.1002/cbic.202400621

Emmanouil Giotas, Stavroula Aikaterini Kaplani, Nikolaos Eleftheriadis

{"title":"The Multifunctional Preprotein Binding Domain of SecA","authors":"Emmanouil Giotas, Stavroula Aikaterini Kaplani, Nikolaos Eleftheriadis","doi":"10.1002/cbic.202400621","DOIUrl":"https://doi.org/10.1002/cbic.202400621","url":null,"abstract":"Sec‐pathway is the main protein secretion pathway in prokaryotes and is essential for their survival. The motor protein SecA is the main coordinator of the pathway in bacteria as it is has evolved to perform multiple tasks, acting like a “swiss army knife”, from binding pre‐proteins to altering its oligomeric and conformational states. This study focuses on the role of its Preprotein Binding Domain (PBD), which is a key protein module that identified in three conformational states (WO, O and C). A thorough analysis was conducted to identify PBD’s inter‐ and intra‐protomeric interactions, highlighting the most significant and conserved ones. Both crystallographic and biophysical data indicate that the WO state is the main during dimerization, while the monomeric structure can adopt all three states. C‐tail, StemPBD and 3β‐tipPBD are important elements for the stabilization of different oligomeric and conformational states, as they offer specific interactions. Alterations in the lipophilicity of the StemPBD causes increased proteins dynamics or/and Prl phenotype. In the C state, 3β‐tipPBD interacts and opens the ATPase motor. We hypothesize that this partial opening of the motor with the increased dynamics describes the Prl phenotype.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142256893","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