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Forty sites of TRP channel regulation 40个TRP通道调控位点
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-11-30 DOI: 10.1016/j.cbpa.2024.102550
Irina A. Talyzina, Kirill D. Nadezhdin, Alexander I. Sobolevsky
{"title":"Forty sites of TRP channel regulation","authors":"Irina A. Talyzina,&nbsp;Kirill D. Nadezhdin,&nbsp;Alexander I. Sobolevsky","doi":"10.1016/j.cbpa.2024.102550","DOIUrl":"10.1016/j.cbpa.2024.102550","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102550"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic ion channels made of DNA 由DNA合成的离子通道。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-31 DOI: 10.1016/j.cbpa.2024.102567
Ran Tivony
{"title":"Synthetic ion channels made of DNA","authors":"Ran Tivony","doi":"10.1016/j.cbpa.2024.102567","DOIUrl":"10.1016/j.cbpa.2024.102567","url":null,"abstract":"<div><div>Natural ion channels have long inspired the design of synthetic nanopores with protein-like features. A significant leap towards this endeavor has been made possible using DNA origami. The exploitation of DNA as a building material has enabled the construction of biomimetic DNA nanopores with a range of pore dimensions and stimuli-responsive capabilities. However, structural fluctuations and ion leakage across the walls of DNA nanopores greatly limit their use in various applications like label-free sensing and as a research tool in functional studies of ion channels. This review outlines some of the guiding principles for biomimetic engineering of DNA-based ion channels, discusses the weaknesses of current DNA nanopore designs, and presents recent efforts to alleviate these limitations.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102567"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Microbial metabolism of host-derived antioxidants 宿主来源抗氧化剂的微生物代谢。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1016/j.cbpa.2024.102565
Zhe Zhou , Stavroula K. Hatzios
{"title":"Microbial metabolism of host-derived antioxidants","authors":"Zhe Zhou ,&nbsp;Stavroula K. Hatzios","doi":"10.1016/j.cbpa.2024.102565","DOIUrl":"10.1016/j.cbpa.2024.102565","url":null,"abstract":"<div><div>Humans are exposed to a wide variety of small molecules with antioxidant properties that are poorly metabolized by mammalian cells. However, gastrointestinal microbes encode enzymes that convert these redox-active molecules into nutrient sources and electron acceptors to support bacterial growth in the gut. Here, we describe recent studies highlighting how microbial metabolism of host-derived antioxidants modulates interspecies interactions and provide an overview of the interdisciplinary approaches being used to map these metabolic pathways <em>in vivo</em>. Uncovering microbe-driven biotransformations of redox-active small molecules could create new opportunities to improve human health by modulating redox reactions at the host–microbe interface.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102565"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Development of novel indicators and molecular systems for calcium sensing through protein engineering 利用蛋白质工程开发新的钙传感指标和分子系统。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2024-12-04 DOI: 10.1016/j.cbpa.2024.102547
Alicia Climent-Catala, Mateo I. Sanchez
{"title":"Development of novel indicators and molecular systems for calcium sensing through protein engineering","authors":"Alicia Climent-Catala,&nbsp;Mateo I. Sanchez","doi":"10.1016/j.cbpa.2024.102547","DOIUrl":"10.1016/j.cbpa.2024.102547","url":null,"abstract":"<div><div>Intracellular calcium (Ca<sup>2+</sup>) is involved in a plethora of cell signalling processes and physiological functions. Increases in Ca<sup>2+</sup> concentration are <em>bona fide</em> biomarkers of neuronal activity, reflecting the spike count, timing, frequency, and the intensity of synaptic input. The development of genetically encoded calcium indicators (GECIs) was a significant advancement in modern neuroscience that enabled real-time visualisation of neuronal activity at single-cell resolution. These indicators leverage the conformational changes induced by calcium-binding proteins, such as calmodulin (CaM) or troponin C (TnC). Harnessing protein engineering approaches such as directed evolution yielded new GECIs with enhanced sensitivity, kinetics, and brightness. Notably, the development of calcium-based integrators, such as scFLARE (single-chain fast light- and activity-regulated expression), convert transient raises in cytosolic Ca<sup>2+</sup> into a transcriptional readout rather than an optical signal. This review summarises the latest efforts in protein engineering to develop new indicators and molecular systems to sense changes in Ca<sup>2+</sup> concentrations.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102547"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142783566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic peptide scaffolds as ion channels and molecular carriers 合成多肽支架作为离子通道和分子载体。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 Epub Date: 2025-01-07 DOI: 10.1016/j.cbpa.2024.102563
Manuel Pérez-Pérez, Alberto Fuertes, Javier Montenegro
{"title":"Synthetic peptide scaffolds as ion channels and molecular carriers","authors":"Manuel Pérez-Pérez,&nbsp;Alberto Fuertes,&nbsp;Javier Montenegro","doi":"10.1016/j.cbpa.2024.102563","DOIUrl":"10.1016/j.cbpa.2024.102563","url":null,"abstract":"<div><div>Transmembrane ion exchange controls biological functions and is essential for life. Over the years, a great variety of nature-inspired artificial ion channels and carriers have been synthesized to control and promote ion exchange across biological membranes. In this context, peptides emerged as ideal scaffolds for synthetic ion channels due to their biocompatibility, accessibility and chemical versatility. Peptides have already shown their potential for the construction of a range of synthetic ion transporters either alone or in combination with other molecular scaffolds. Among the great diversity of peptide-based ion transporters, we can find key examples of single-molecule and supramolecular transmembrane ion channels and ionophores. Peptide scaffolds have also found great potential for the transmembrane delivery of biomolecular cargos such as nucleic acids and proteins. This review covers some of the most relevant advances in the peptide-based ion transport field from the last few years.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102563"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synthetic transporters for oxoanions 氧阴离子合成转运体。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-11-14 DOI: 10.1016/j.cbpa.2024.102542
Karolis Norvaisa, Aaron Torres-Huerta, Hennie Valkenier
{"title":"Synthetic transporters for oxoanions","authors":"Karolis Norvaisa,&nbsp;Aaron Torres-Huerta,&nbsp;Hennie Valkenier","doi":"10.1016/j.cbpa.2024.102542","DOIUrl":"10.1016/j.cbpa.2024.102542","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102542"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Endogenous electrophiles and peroxymonocarbonate can link tyrosine phosphorylation cascades with the cytosolic TXNRD1 selenoprotein and the KEAP1/NRF2 system 内源性亲电子物和过氧碳酸氢盐可将酪氨酸磷酸化级联与细胞质 TXNRD1 硒蛋白和 KEAP1/NRF2 系统联系起来。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-09-06 DOI: 10.1016/j.cbpa.2024.102522
Markus Dagnell , Elias S.J. Arnér
{"title":"Endogenous electrophiles and peroxymonocarbonate can link tyrosine phosphorylation cascades with the cytosolic TXNRD1 selenoprotein and the KEAP1/NRF2 system","authors":"Markus Dagnell ,&nbsp;Elias S.J. Arnér","doi":"10.1016/j.cbpa.2024.102522","DOIUrl":"10.1016/j.cbpa.2024.102522","url":null,"abstract":"<div><p>Endogenously formed reactive molecules, such as lipid peroxides, 4-hydroxynonenal, methylglyoxal and other reactive oxygen species, can have major effects on cells. Accumulation of these molecules is counteracted by antioxidant enzymes, including the glutathione (GSH) and thioredoxin (Trx) systems, in turn regulated by the KEAP1/NRF2 system. Receptor tyrosine kinases (RTK) and their counteracting protein tyrosine phosphatases (PTP) are also modulated through redox regulation of PTP activities. The cytosolic selenoprotein thioredoxin reductase (TXNRD1) is particularly prone to attack at its easily accessible catalytic selenocysteine (Sec) residue by reactive electrophilic compounds. Therefore, we here discuss how endogenously formed electrophiles can modulate RTK/PTP signaling in a concentration- and time dependent manner by reactions either directly or indirectly linking TXNRD1 with the KEAP1/NRF2 system. Moreover, recent findings suggest that endogenous formation of peroxymonocarbonate can efficiently inhibit PTP activities and stimulate RTK signaling, seemingly bypassing PTP reduction as otherwise supported by the GSH/Trx systems.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102522"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136759312400098X/pdfft?md5=a310db9e055eef46580e7b9e5c96a3b4&pid=1-s2.0-S136759312400098X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond chloroquine: Cationic amphiphilic drugs as endosomal escape enhancers for nucleic acid therapeutics 超越氯喹：阳离子两亲药物作为核酸治疗药物的内体逸出增强剂。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-10-05 DOI: 10.1016/j.cbpa.2024.102531
Aliona Debisschop , Bram Bogaert , Cristina Muntean , Stefaan C. De Smedt , Koen Raemdonck
{"title":"Beyond chloroquine: Cationic amphiphilic drugs as endosomal escape enhancers for nucleic acid therapeutics","authors":"Aliona Debisschop ,&nbsp;Bram Bogaert ,&nbsp;Cristina Muntean ,&nbsp;Stefaan C. De Smedt ,&nbsp;Koen Raemdonck","doi":"10.1016/j.cbpa.2024.102531","DOIUrl":"10.1016/j.cbpa.2024.102531","url":null,"abstract":"<div><div>Nucleic acid (NA) therapeutics have the potential to treat or prevent a myriad of diseases but generally require cytosolic delivery to be functional. NA drugs are therefore often encapsulated into delivery systems that mediate effective endocytic uptake by target cells, but unfortunately often display limited endosomal escape efficiency. This review will focus on the potential of repurposing cationic amphiphilic drugs (CADs) to enhance endosomal escape. In general terms, CADs are small molecules with one or more hydrophobic groups and a polar domain containing a basic amine. CADs have been reported to accumulate in acidified intracellular compartments (e.g., endosomes and lysosomes), integrate in cellular membranes and alter endosomal trafficking pathways, ultimately resulting in improved cytosolic release of the endocytosed cargo. As many CADs are widely used drugs, their repurposing offers opportunities for combination therapies with NAs.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102531"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-10-25 DOI: 10.1016/j.cbpa.2024.102539
Pamela V. Chang
{"title":"Microbial metabolite-receptor interactions in the gut microbiome","authors":"Pamela V. Chang","doi":"10.1016/j.cbpa.2024.102539","DOIUrl":"10.1016/j.cbpa.2024.102539","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102539"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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
Current Opinion in Chemical Biology Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI: 10.1016/j.cbpa.2024.102543
Yuichi Shichino , Shintaro Iwasaki
{"title":"Corrigendum to “Compounds for selective translational inhibition” [Curr Opin Chem Biol 69 (2022) 102158]","authors":"Yuichi Shichino ,&nbsp;Shintaro Iwasaki","doi":"10.1016/j.cbpa.2024.102543","DOIUrl":"10.1016/j.cbpa.2024.102543","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"83 ","pages":"Article 102543"},"PeriodicalIF":6.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
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