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Probing ligand-induced local stability shifts: A sensitive approach to identify target proteins and binding sites at the proteomic scale 探测配体诱导的局部稳定性转移:一种在蛋白质组学尺度上识别靶蛋白和结合位点的敏感方法
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-31 DOI: 10.1016/j.cbpa.2025.102602
Keyun Wang , Yanan Li , Yanni Ma , Mingliang Ye
Deciphering ligand-induced structural alterations represents a critical frontier in functional proteomics, offering transformative potential for both target identification and mechanistic understanding of ligand actions. Therefore, it is of great interest to develop robust proteomic approaches to uncover the binding relationship between ligands and the targeting proteins. The ligand modification-free approaches have the advantages of bypassing chemical modification and thus are broadly applicable to diverse ligands. Herein, in this review, we will introduce some recent methodology advancements for modification-free approaches in the identification of interactions between ligands and proteins. Especially, we will focus on a newly developed method, peptide-centric local stability assay (PELSA), which was designed to probe the ligand-induced local stability shifts and was demonstrated to have high sensitivity in revealing the binding regions at proteome level. The continued refinement and wider implementation of such technologies are expected to revolutionize fundamental research related with ligand–protein interactions.
破译配体诱导的结构改变是功能蛋白质组学的一个关键前沿,为目标识别和配体作用的机制理解提供了变革潜力。因此,开发强大的蛋白质组学方法来揭示配体与靶蛋白之间的结合关系是非常有意义的。无配体修饰的方法具有绕过化学修饰的优点,因此广泛适用于各种配体。在这篇综述中,我们将介绍一些最新的无修饰方法在鉴定配体和蛋白质之间相互作用方面的进展。特别是,我们将重点关注一种新开发的方法,肽中心局部稳定性测定(PELSA),该方法旨在探测配体诱导的局部稳定性变化,并被证明在蛋白质组水平上揭示结合区域具有很高的灵敏度。这些技术的不断完善和更广泛的实施有望彻底改变与配体-蛋白质相互作用相关的基础研究。
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引用次数: 0
Natural and artificial siderophores: Iron-based applications and beyond 天然和人工铁载体:铁基应用及其他
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-23 DOI: 10.1016/j.cbpa.2025.102601
Zih-Jheng Lin, Cheng-Yu Fang, Tsung-Shing Andrew Wang
Siderophores are iron chelators secreted by microorganisms to scavenge iron from the environment. Natural siderophores have gained remarkable importance because their conjugates can be applied as antibiotics and diagnostic imaging agents. By utilizing the iron uptake system of microorganisms, functional molecules such as antibiotics or imaging agents can be delivered into cells. Notably, artificial siderophores have also been developed to increase stability and broaden metal chelating diversity. Various strategies, including backbone fine-tuning, artificial chelation moieties, and direct metal swapping, can be employed. Therefore, artificial siderophores can bind biorelated metals or radioactive isotopes, expanding their biological and medical applications. The aim of this review is to introduce recent advances in natural and artificial siderophore applications and highlight future challenges in this area of research.
铁载体是由微生物分泌的铁螯合剂,用于清除环境中的铁。天然铁载体具有显著的重要性,因为它们的偶联物可以用作抗生素和诊断显像剂。利用微生物的铁摄取系统,可以将抗生素或显像剂等功能分子输送到细胞中。值得注意的是,人工铁载体也被开发出来,以提高稳定性和扩大金属螯合的多样性。可以采用各种策略,包括骨干微调、人工螯合部分和直接金属交换。因此,人工铁载体可以结合生物相关金属或放射性同位素,扩大其生物和医学应用。本文综述了天然和人工铁载体应用的最新进展,并强调了该研究领域未来的挑战。
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引用次数: 0
Recent developments in probing the levels and flux of selected organellar cations as well as organellar mechanosensitivity 在探测选定的细胞器阳离子的水平和通量以及细胞器的机械敏感性方面的最新进展
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-05-03 DOI: 10.1016/j.cbpa.2025.102600
Taufiq Rahman , Sandip Patel
Electrochemical gradients exist not only across the plasma membrane (PM) but also across membranes of organelles. Various endomembrane-localised ion channels and transporters have been identified, the activity of which is critical for organellar (and also cellular) ionic homeostasis that underpins diverse cellular processes. Aberrant organellar ion flux underlies several diseases, identifying organellar channels and transporters as potential drug targets. Therefore, the need for probing the functions of these proteins in situ cannot be overemphasised. The acidic interior of a few organelles as well as the dynamic nature of most organelles historically presented challenges for reliable estimation of luminal ionic concentrations. But there have been significant methodological and technical advancements by now, allowing measurement of levels of specific ions within these organelles as well as their flux across endomembranes with increasing precision. Evidence also continues to amass reporting mechanosensitivity of the endomembranes and its physiological significance. Here we highlight some recent developments in tools and techniques for measuring the levels and movement of some selected organellar cations as well as organellar mechanosensitivity.
电化学梯度不仅存在于质膜上,也存在于细胞器膜上。已经确定了各种膜局部离子通道和转运体,其活性对于支持多种细胞过程的细胞器(和细胞)离子稳态至关重要。异常的细胞器离子通量是几种疾病的基础,确定了细胞器通道和转运体作为潜在的药物靶点。因此,原位探测这些蛋白质功能的必要性再怎么强调也不为过。一些细胞器的酸性内部以及大多数细胞器的动态性质历来为可靠估计腔内离子浓度提出了挑战。但是到目前为止,已经有了重大的方法和技术进步,可以越来越精确地测量这些细胞器内特定离子的水平以及它们穿过内膜的通量。关于膜的机械敏感性及其生理意义的报道也越来越多。在这里,我们重点介绍了一些工具和技术的最新发展,用于测量一些选定的细胞器阳离子的水平和运动以及细胞器的机械敏感性。
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引用次数: 0
Editorial overview: Transforming intracellular delivery: Innovations in macromolecule transport 编辑概述:转化细胞内递送:大分子运输的创新
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-28 DOI: 10.1016/j.cbpa.2025.102599
Jean-Philippe Pellois
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引用次数: 0
Editorial: Unusual enzyme reactions in natural products biosynthesis 社论:天然产物生物合成中不寻常的酶反应
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-26 DOI: 10.1016/j.cbpa.2025.102597
Taifo Mahmud, Ikuro Abe
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引用次数: 0
Chemical strategies for targeting lipid pathways in bacterial pathogens 针对细菌病原体脂质途径的化学策略
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-19 DOI: 10.1016/j.cbpa.2025.102596
Alyssa M. Carter , Emily C. Woods , Matthew Bogyo
Microbial pathogens continue to plague human health and develop resistance to our current frontline treatments. Over the last few decades, there has been limited development of antibiotics with new mechanisms of action, highlighting our need to identify processes that can be targeted by next generation therapeutics. Recent advancements in our understanding of the roles that lipids play in key bacterial processes suggest that these biomolecules are a potentially valuable site for disruption by therapeutic agents. Specifically, the success of a pathogen depends on its ability to make fatty acids de novo or scavenge lipids from its host. This review focuses on recent advances using chemical biology tools for defining and disrupting lipid pathways in bacteria.
微生物病原体继续困扰着人类健康,并对我们目前的一线治疗产生耐药性。在过去的几十年里,具有新的作用机制的抗生素的发展有限,这突出了我们需要确定下一代治疗方法可以针对的过程。最近我们对脂质在关键细菌过程中所起作用的理解取得了进展,这表明这些生物分子是治疗剂破坏的潜在有价值的位点。具体来说,病原体的成功取决于其重新生成脂肪酸或清除宿主脂质的能力。本文综述了利用化学生物学工具定义和破坏细菌脂质途径的最新进展。
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引用次数: 0
Molecular and biochemical insights from natural and engineered photosynthetic endosymbiotic systems 从自然和工程光合内共生系统的分子和生化见解
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-18 DOI: 10.1016/j.cbpa.2025.102598
Jay E. Cournoyer , Bidhan C. De , Angad P. Mehta
Mitochondria and chloroplasts evolved through the transformation of bacterial endosymbionts established within the host cells. Studies on these organelles have provided several phylogenetic and biochemical insights related to this remarkable evolutionary transformation. Additionally, comparative studies between naturally existing endosymbionts and present-day organelles have allowed us to identify important common features of endosymbiotic evolution. In this review, we discuss hallmarks of photosynthetic endosymbiotic systems, particularly focusing on some of the fascinating molecular changes that occur in the endosymbiont and the host as the endosymbiont/host chimera evolves and transforms endosymbionts into organelles; these include the following: (i) endosymbiont genome minimization and host/endosymbiont gene transfer, (ii) protein import/export systems, (iii) metabolic crosstalk between the endosymbiont, (iv) alterations to the endosymbiont peptidoglycan, and (v) host-controlled replication of endosymbionts/organelles. We discuss these hallmarks in the context of naturally existing photosynthetic endosymbiotic systems and present-day chloroplasts. Further, we also briefly discuss laboratory efforts to engineer endosymbiosis between photosynthetic bacteria and host cells, the lessons learned from these studies, future directions of these studies, and their implications on evolutionary biology and synthetic biology.
线粒体和叶绿体通过在宿主细胞内建立的细菌内共生体的转化而进化。对这些细胞器的研究提供了与这种显著的进化转变有关的几种系统发育和生化见解。此外,自然存在的内共生生物和当今的细胞器之间的比较研究使我们能够确定内共生进化的重要共同特征。在这篇综述中,我们讨论了光合内共生系统的特征,特别关注了随着内共生体/宿主嵌合体的进化和将内共生体转化为细胞器而发生在内共生体和宿主体内的一些有趣的分子变化;这些包括以下内容:(i)内共生体基因组最小化和宿主/内共生体基因转移,(ii)蛋白质输入/输出系统,(iii)内共生体之间的代谢串音,(iv)内共生体肽聚糖的改变,以及(v)宿主控制的内共生体/细胞器的复制。我们在自然存在的光合内共生系统和当今的叶绿体的背景下讨论这些标志。此外,我们还简要讨论了实验室在设计光合细菌与宿主细胞之间的内共生方面所做的努力,从这些研究中获得的经验教训,这些研究的未来方向,以及它们对进化生物学和合成生物学的影响。
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引用次数: 0
Opportunities in exploring chemical biology tools for better strategies against Candida albicans 探索化学生物学工具的机会,以更好地对抗白色念珠菌
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-04-04 DOI: 10.1016/j.cbpa.2025.102595
Lanxin Li, Yuan Qiao
The growing global prevalence of drug-resistant fungal infections and the scarcity of effective clinical antifungal drugs necessitate an urgent need for new treatments and strategies. In the quest for novel antifungal and anti-virulence compounds and alternative drug targets in fungi, we recognize the significant value of chemical biology tools in guiding these endeavors. Focusing on Candida albicans, the major fungal pathogen in humans, this review explores recent antifungal research efforts that utilize chemical biology tools—such as chemical probes and toolkits—that offer valuable biological insights into the cellular processes of C. albicans. In addition, we discuss the wealth of compounds in the host gut microbiota that naturally influence C. albicans invasive growth in the gut habitat, presenting promising yet underexplored opportunities for developing novel antifungal and anti-virulence strategies. Chemical biology tools are uniquely positioned to unlock the potential of gut microbiota-derived molecules and metabolites in combating C. albicans infections.
全球耐药真菌感染的日益流行和有效的临床抗真菌药物的缺乏迫切需要新的治疗方法和策略。在寻找新的抗真菌和抗毒化合物和真菌替代药物靶点的过程中,我们认识到化学生物学工具在指导这些努力中的重要价值。针对人类主要的真菌病原体白色念珠菌,本文综述了近年来利用化学生物学工具(如化学探针和工具箱)进行抗真菌研究的成果,这些研究为白色念珠菌的细胞过程提供了有价值的生物学见解。此外,我们讨论了宿主肠道微生物群中丰富的化合物,这些化合物自然影响白色念珠菌在肠道栖息地的侵袭性生长,为开发新的抗真菌和抗毒策略提供了有希望但尚未开发的机会。化学生物学工具具有独特的定位,可以释放肠道微生物衍生分子和代谢物在对抗白色念珠菌感染方面的潜力。
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引用次数: 0
Corrigendum to “Bacterial diterpene synthases: New opportunities for mechanistic enzymology and engineered biosynthesis” [Curr Opin Chem Biol, 16 (2012) 132–141 “细菌二萜合成酶:机械酶学和工程生物合成的新机遇”的更正[当前观点化学生物,16 (2012)132-141
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-26 DOI: 10.1016/j.cbpa.2025.102594
Michael J. Smanski , Ryan M. Peterson , Sheng-Xiong Huang , Ben Shen
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引用次数: 0
Recent advances in de novo designed metallopeptides as tailored enzyme mimics 重新设计金属肽作为定制酶模拟物的最新进展。
IF 6.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.cbpa.2025.102586
Salvatore La Gatta, Vincent L. Pecoraro
Advances in de novo design of metallopeptides have paved the way for customized metalloenzyme mimics with impressive catalytic capabilities. Over the last few years, incorporation of transition metals into simplified peptide scaffolds has allowed for catalytic efficiencies similar to or greater than those found in natural metalloenzymes. Artificial de novo peptide scaffolds highlight how precise modifications to metal coordination environments can improve scaffold stability and catalytic efficiency for a wide range of applications towards redox, non redox, synthetic, and energy conversion chemistry. These insights deepen our understanding of enzyme evolution and set a solid foundation for new directions in biocatalysis.
金属肽从头设计的进步为具有令人印象深刻的催化能力的定制金属酶模拟物铺平了道路。在过去的几年中,将过渡金属结合到简化肽支架中,使得催化效率与天然金属酶相似或更高。人工肽支架强调了对金属配位环境的精确修饰如何提高支架的稳定性和催化效率,在氧化还原、非氧化还原、合成和能量转换化学方面有着广泛的应用。这些发现加深了我们对酶进化的理解,为生物催化的新方向奠定了坚实的基础。
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引用次数: 0
期刊
Current Opinion in Chemical Biology
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