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Discovering microbiota functions via chemical probe incorporation for targeted sequencing 通过化学探针结合发现微生物群功能，用于靶向测序
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102551
Natalie Falco , Matthew E. Griffin
Our microbiota plays crucial roles in immune development and homeostasis and has been implicated in virtually all major diseases of the 21st century. Nevertheless, our understanding of the exact microbial functions that underlie these correlations remains extremely limited, due in large part to the difficulty of profiling cellular activities within non-model organisms and complex communities. Over the past decade, new flow cytometric approaches have been developed to distinguish specific microbial populations based on their interactions with metabolite analogs, modified biomolecules, and reactive compounds. By selecting and separating active microbes via fluorescence-activated cell sorting, PRobe INcorporation for Targeted sequencing (PRINT-seq) has inspired innovative approaches to identify and characterize functional members of our microbiota. Here, we provide a broad overview of this evolving technology and summarize how this method has been recently employed as a diagnostic fingerprint for diverse microbial activities.
我们的微生物群在免疫发育和体内平衡中起着至关重要的作用，并与21世纪几乎所有主要疾病有关。然而，我们对这些相关性背后的确切微生物功能的理解仍然非常有限，这在很大程度上是由于在非模式生物和复杂群落中分析细胞活动的困难。在过去的十年里，新的流式细胞术方法已经被开发出来，根据它们与代谢物类似物、修饰生物分子和活性化合物的相互作用来区分特定的微生物种群。通过荧光活化细胞分选选择和分离活性微生物，PRobe incorporated for Targeted sequencing （PRINT-seq）激发了识别和表征微生物群功能成员的创新方法。在这里，我们提供了这种不断发展的技术的广泛概述，并总结了这种方法最近如何被用作多种微生物活动的诊断指纹。
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引用次数: 0
Forty sites of TRP channel regulation 40个TRP通道调控位点
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-30 DOI: 10.1016/j.cbpa.2024.102550
Irina A. Talyzina, Kirill D. Nadezhdin, Alexander I. Sobolevsky
Transient receptor potential (TRP) channels are polymodal molecular sensors that integrate chemical, thermal, mechanical and electrical stimuli and convert them into ionic currents that regulate senses of taste, smell, vision, hearing, touch and contribute to perception of temperature and pain. TRP channels are implicated in the pathogenesis of numerous human diseases, including cancers, and represent one of the most ardently pursued drug targets. Recent advances in structural biology, particularly associated with the cryo-EM “resolution revolution”, yielded numerous TRP channel structures in complex with ligands that might have therapeutic potential. In this review, we describe the recent progress in TRP channel structural biology, focusing on the description of identified binding sites for small molecules, their relationship to membrane lipids, and interaction of TRP channels with other proteins. The characterized binding sites and interfaces create a diversity of druggable targets and provide a roadmap to aid in the design of new molecules for tuning TRP channel function in disease conditions.
瞬态受体电位（TRP）通道是多模态分子传感器，整合化学、热、机械和电刺激，并将其转化为离子电流，调节味觉、嗅觉、视觉、听觉、触觉，并有助于感知温度和疼痛。色氨酸通道与包括癌症在内的许多人类疾病的发病机制有关，是最受关注的药物靶点之一。结构生物学的最新进展，特别是与低温电镜“分辨率革命”相关的进展，产生了许多与配体复合物的TRP通道结构，这些结构可能具有治疗潜力。本文综述了TRP通道结构生物学的最新进展，重点介绍了小分子结合位点的描述、它们与膜脂的关系以及TRP通道与其他蛋白质的相互作用。表征的结合位点和界面创造了多种可药物靶点，并为帮助设计在疾病条件下调节TRP通道功能的新分子提供了路线图。
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引用次数: 0
Corrigendum to “Drug discovery targeting Nav1.8: Structural insights and therapeutic potential” [Curr Opin Chem Biol 83 (2024) 102538] 针对 Nav1.8 的药物发现：结构见解和治疗潜力》[Curr Opin Chem Biol 83 (2024) 102538] 更正
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102546
Huan Wang , Jian Huang , Jie Zang , Xueqin Jin , Nieng Yan
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引用次数: 0
Engineered metallobiocatalysts for energy–relevant reactions 用于能源相关反应的工程金属生物催化剂
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-25 DOI: 10.1016/j.cbpa.2024.102545
Ryan M. Kosko , Kaye L. Kuphal , Alison A. Salamatian , Kara L. Bren
Engineering metallobiocatalysts is a promising approach to addressing challenges in energy-relevant electrocatalysis and photocatalysis. The design freedom provided by semisynthetic and fully synthetic approaches to catalyst design allows researchers to demonstrate how structural modifications can improve selectivity and activity of biocatalysts. Furthermore, the provision of a superstructure in many metallobiocatalysts facilitates active-site microenvironment engineering. Recurring themes include the role of the biomolecular scaffold in enhancing reactivity in water and catalyst robustness, the impact of the outer sphere on reactivity, and the importance of tuning system components in full system optimization. In this perspective, recent strategies to design and modify novel biocatalysts, understand proton and electron transfer mechanisms, and tune system activity by modifying catalysts and system conditions are highlighted within the field of energy-related catalysis. Opportunities in this field include developing robust structure–function relationships to support approaches to engineering second-sphere interactions and identifying ways to enhance biocatalyst activity over time.
设计金属生物催化剂是应对能源相关电催化和光催化挑战的一种前景广阔的方法。半合成和全合成催化剂设计方法所提供的设计自由度使研究人员能够展示结构修饰如何提高生物催化剂的选择性和活性。此外，许多金属生物催化剂都具有上层结构，这为活性位点微环境工程提供了便利。反复出现的主题包括生物分子支架在提高水中反应性和催化剂稳健性方面的作用、外球对反应性的影响以及在整个系统优化过程中调整系统组分的重要性。从这个角度出发，重点介绍了在能源相关催化领域设计和改造新型生物催化剂、了解质子和电子转移机制以及通过改造催化剂和系统条件来调整系统活性的最新策略。该领域的机遇包括发展稳健的结构-功能关系，以支持第二球相互作用的工程学方法，以及确定随着时间推移增强生物催化剂活性的方法。
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引用次数: 0
Synthetic ion channels in biomembranes 生物膜中的合成离子通道。
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-20 DOI: 10.1016/j.cbpa.2024.102544
Ai Kohata , Kazushi Kinbara
Ion transport across cell membranes is crucial in maintaining ion homeostasis in cells. Synthetic molecules that can mimic the functions of natural ion channel proteins would possess great potential as therapeutic agents by promoting apoptosis or interfering with autophagic processes through perturbing the intracellular pH or inducing oxidative and osmotic stresses. However, little is known about the underlying mechanisms in terms of direct correlation between ion transport and biological functions. This review summarizes recent progress in the area of synthetic transmembrane ion transport systems, focusing on the channel type, with an emphasis on their bioapplications as anticancer agents.
离子在细胞膜上的转运是维持细胞离子平衡的关键。能模拟天然离子通道蛋白功能的合成分子通过扰乱细胞内 pH 值或诱导氧化和渗透压力，促进细胞凋亡或干扰自噬过程，具有很大的治疗潜力。然而，人们对离子转运与生物功能直接相关的内在机制知之甚少。本综述总结了合成跨膜离子转运系统领域的最新进展，重点是通道类型，并着重介绍了它们作为抗癌剂的生物应用。
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引用次数: 0
Transferring enzyme features to molecular CO2 reduction catalysts 将酶的特性转化为分子二氧化碳还原催化剂。
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-15 DOI: 10.1016/j.cbpa.2024.102540
Matthias Huber, Corinna R. Hess
Carbon monoxide dehydrogenases and formate dehydrogenases efficiently catalyze the reduction of CO2. In both enzymes, CO2 activation at the metal active site is assisted by proximate amino acids and Fe–S-clusters. Functional features of the enzyme are mimicked in molecular catalysts by redox-active ligands, acidic and charged groups in the ligand periphery, and binuclear scaffolds. These components have all improved the catalytic performance of synthetic systems. Recent studies impart a deeper understanding of the individual contributions of the various functionalities to reactivity and of their combined effects. New catalyst platforms reveal alternate pathways for CO2 reduction, unique intermediates, and strategies for switching selectivity. Design of a wider array of complexes that combine different functional elements is encouraged to further optimize catalysts for CO2 reduction, especially for product formation beyond CO. More diverse bimetallic catalysts are needed to better exploit metal–metal interactions for CO2 conversion.
一氧化碳脱氢酶和甲酸脱氢酶能有效催化二氧化碳还原。在这两种酶中，金属活性位点上的二氧化碳活化都得到了近似氨基酸和 Fe-S 簇的协助。在分子催化剂中，氧化还原活性配体、配体外围的酸性和带电基团以及双核支架可模拟酶的功能特征。这些成分都提高了合成系统的催化性能。最近的研究加深了人们对各种官能团对反应性的单独贡献及其综合效应的理解。新的催化剂平台揭示了二氧化碳还原的替代途径、独特的中间产物以及转换选择性的策略。我们鼓励设计更多结合不同功能元素的复合物，以进一步优化二氧化碳还原催化剂，特别是用于形成二氧化碳以外的产物。需要更多样化的双金属催化剂，以更好地利用金属与金属之间的相互作用进行二氧化碳转化。
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引用次数: 0
Synthetic transporters for oxoanions 氧阴离子合成转运体。
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-14 DOI: 10.1016/j.cbpa.2024.102542
Karolis Norvaisa, Aaron Torres-Huerta, Hennie Valkenier
This brief review highlights recent advances in the transport of oxoanions using synthetic carriers, focusing on both progress and ongoing challenges in the field. The difficulty of transporting these oxoanions increases with their hydration enthalpies, with less hydrated nitrate and perchlorate being relatively easy to transport. Recent progress has focused on the transport of moderately hydrated anions such as bicarbonate and carboxylates, where studies are influenced by the free diffusion of neutral species obtained by (de)protonation equilibria. Despite significant innovations in the design of synthetic carriers, the transport of the highly hydrated oxoanions sulfate and phosphate remains a major challenge. Progress on sulfate transport has stalled, while the first example of phosphate transport was reported only last year.
这篇简短的综述重点介绍了利用合成载体传输氧阴离子的最新进展，重点关注该领域的进展和当前面临的挑战。运输这些氧阴离子的难度随其水化焓的增加而增加，水化程度较低的硝酸盐和高氯酸盐相对容易运输。最近的研究进展主要集中在中度水合阴离子（如碳酸氢盐和羧酸盐）的迁移上，其研究受到了通过（去）质子化平衡获得的中性物质自由扩散的影响。尽管在合成载体的设计方面取得了重大创新，但硫酸根和磷酸根等高水合氧阴离子的传输仍然是一项重大挑战。硫酸盐迁移方面的研究进展停滞不前，而磷酸盐迁移方面的第一个实例直到去年才有报道。
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引用次数: 0
Corrigendum to “Compounds for selective translational inhibition” [Curr Opin Chem Biol 69 (2022) 102158] 对 "选择性翻译抑制化合物 "的更正 [Curr Opin Chem Biol 69 (2022) 102158]
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-06 DOI: 10.1016/j.cbpa.2024.102543
Yuichi Shichino , Shintaro Iwasaki
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引用次数: 0
Designing small-molecule and macromolecule sensors for imaging redox-active transition metal signaling 设计用于成像氧化还原活性过渡金属信号的小分子和大分子传感器
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-11-04 DOI: 10.1016/j.cbpa.2024.102541
Aidan T. Pezacki , Jiaying Gao , Christopher J. Chang
Transition metals play essential roles in biology, where these nutrients regulate protein activity as active site cofactors or via metalloallostery. In contrast, dysregulation of transition metal homeostasis can lead to unique metal-dependent signaling pathways connected to aging and disease, such as cuproptosis and ferroptosis for copper- and iron-dependent cell death or cuproplasia and ferroplasia for copper- and iron-dependent cell growth and proliferation, respectively. New methods that enable detection of bioavailable transition metal pools with both metal and oxidation state specificity can help decipher their contributions to health and disease. Here we summarize recent advances in designing sensors for imaging transition metals and their applications to uncover new metal biology.
过渡金属在生物学中发挥着至关重要的作用，这些营养物质作为活性位点辅助因子或通过金属变质作用调节蛋白质的活性。相反，过渡金属平衡失调会导致与衰老和疾病相关的独特的金属依赖性信号通路，如杯突症和铁突症分别导致铜和铁依赖性细胞死亡，或杯增生和铁增生分别导致铜和铁依赖性细胞生长和增殖。采用新方法检测具有金属和氧化态特异性的生物可利用过渡金属池，有助于破解它们对健康和疾病的影响。在此，我们总结了设计过渡金属成像传感器的最新进展及其在揭示新金属生物学方面的应用。
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引用次数: 0
Microbial metabolite-receptor interactions in the gut microbiome 肠道微生物群中微生物代谢物与受体之间的相互作用。
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Current Opinion in Chemical Biology
Pub Date : 2024-10-25 DOI: 10.1016/j.cbpa.2024.102539
Pamela V. Chang
The gut microbiome impacts many physiological processes that greatly influence host health and disease. Metabolites produced by the gut microbiota have emerged as central players in regulating these biological pathways, often through the engagement of specific host receptors. Despite the importance of these microbial metabolites and receptors in human biology, the vast majority of these interactions remain uncharted due to the complex nature of the gut microbiome and the multitude of metabolites that these microbes produce. Here, we highlight recent developments in identifying such host-gut microbiota interactions, including characterization of bioactive metabolites and their mechanisms of action. Understanding these pathways will enable the development of prophylactics and therapeutics for treating many inflammatory diseases that are impacted by the gut microbiota.
肠道微生物群影响着许多生理过程，对宿主的健康和疾病有很大影响。肠道微生物群产生的代谢物已成为调节这些生物通路的核心角色，通常是通过与特定的宿主受体相互作用来实现的。尽管这些微生物代谢物和受体在人类生物学中非常重要，但由于肠道微生物群的复杂性和这些微生物产生的大量代谢物，这些相互作用中的绝大部分仍是未知的。在此，我们将重点介绍在确定这种宿主-肠道微生物群相互作用方面的最新进展，包括生物活性代谢物的特征及其作用机制。了解这些途径将有助于开发预防和治疗药物，以治疗受肠道微生物群影响的多种炎症性疾病。
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引用次数: 0
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