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Ligand discovery by activity-based protein profiling 通过基于活性的蛋白质分析发现配体
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.006
Micah J. Niphakis , Benjamin F. Cravatt
{"title":"Ligand discovery by activity-based protein profiling","authors":"Micah J. Niphakis ,&nbsp;Benjamin F. Cravatt","doi":"10.1016/j.chembiol.2024.08.006","DOIUrl":"10.1016/j.chembiol.2024.08.006","url":null,"abstract":"<div><p>Genomic technologies have led to massive gains in our understanding of human gene function and disease relevance. Chemical biologists are a primary beneficiary of this information, which can guide the prioritization of proteins for chemical probe and drug development. The vast functional and structural diversity of disease-relevant proteins, however, presents challenges for conventional small molecule screening libraries and assay development that in turn raise questions about the broader “druggability” of the human proteome. Here, we posit that activity-based protein profiling (ABPP), by generating global maps of small molecule-protein interactions in native biological systems, is well positioned to address major obstacles in human biology-guided chemical probe and drug discovery. We will support this viewpoint with case studies highlighting a range of small molecule mechanisms illuminated by ABPP that include the disruption and stabilization of biomolecular (protein-protein/nucleic acid) interactions and underscore allostery as a rich source of chemical tools for historically “undruggable” protein classes.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1636-1651"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Reflections from advisory board members and associate editors 顾问委员会成员和副主编的思考
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.015
Michelle Arkin, Sara Buhrlage, Ling-Ling Chen, Peng Chen, Jason Gestwicki, Chuan He, Gerald F. Joyce, Angela Koehler, Milka Kostic, Jun Liu, Jim Wells
{"title":"Reflections from advisory board members and associate editors","authors":"Michelle Arkin,&nbsp;Sara Buhrlage,&nbsp;Ling-Ling Chen,&nbsp;Peng Chen,&nbsp;Jason Gestwicki,&nbsp;Chuan He,&nbsp;Gerald F. Joyce,&nbsp;Angela Koehler,&nbsp;Milka Kostic,&nbsp;Jun Liu,&nbsp;Jim Wells","doi":"10.1016/j.chembiol.2024.08.015","DOIUrl":"10.1016/j.chembiol.2024.08.015","url":null,"abstract":"<div><p>For the celebration of the 30<sup>th</sup> anniversary of <em>Cell Chemical Biology</em>, in the September special issue, we asked former and current advisory board members and former editors to reflect on the advancements in chemical biology, changes in the field, and their insights into <em>Cell Chemical Biology</em> (originally <em>Chemistry &amp; Biology</em>).</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1557-1561"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003647/pdfft?md5=2f38124a3b76bef314cf59b1accd156a&pid=1-s2.0-S2451945624003647-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Advances in spatial proteomics: Mapping proteome architecture from protein complexes to subcellular localizations 空间蛋白质组学的进展：绘制从蛋白质复合物到亚细胞定位的蛋白质组结构图
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.008
Lisa M. Breckels , Charlotte Hutchings , Kishor D. Ingole , Suyeon Kim , Kathryn S. Lilley , Mehul V. Makwana , Kieran J.A. McCaskie , Eneko Villanueva
{"title":"Advances in spatial proteomics: Mapping proteome architecture from protein complexes to subcellular localizations","authors":"Lisa M. Breckels ,&nbsp;Charlotte Hutchings ,&nbsp;Kishor D. Ingole ,&nbsp;Suyeon Kim ,&nbsp;Kathryn S. Lilley ,&nbsp;Mehul V. Makwana ,&nbsp;Kieran J.A. McCaskie ,&nbsp;Eneko Villanueva","doi":"10.1016/j.chembiol.2024.08.008","DOIUrl":"10.1016/j.chembiol.2024.08.008","url":null,"abstract":"<div><p>Proteins are responsible for most intracellular functions, which they perform as part of higher-order molecular complexes, located within defined subcellular niches. Localization is both dynamic and context specific and mislocalization underlies a multitude of diseases. It is thus vital to be able to measure the components of higher-order protein complexes and their subcellular location dynamically in order to fully understand cell biological processes. Here, we review the current range of highly complementary approaches that determine the subcellular organization of the proteome. We discuss the scale and resolution at which these approaches are best employed and the caveats that should be taken into consideration when applying them. We also look to the future and emerging technologies that are paving the way for a more comprehensive understanding of the functional roles of protein isoforms, which is essential for unraveling the complexities of cell biology and the development of disease treatments.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1665-1687"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400357X/pdfft?md5=d7d9545c4fe5c1529fc55f268dc36ff3&pid=1-s2.0-S245194562400357X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
New therapies on the horizon: Targeted protein degradation in neuroscience 地平线上的新疗法神经科学中的靶向蛋白质降解
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.010
James A. Gregory , Christopher M. Hickey , Juan Chavez , Angela M. Cacace
{"title":"New therapies on the horizon: Targeted protein degradation in neuroscience","authors":"James A. Gregory ,&nbsp;Christopher M. Hickey ,&nbsp;Juan Chavez ,&nbsp;Angela M. Cacace","doi":"10.1016/j.chembiol.2024.08.010","DOIUrl":"10.1016/j.chembiol.2024.08.010","url":null,"abstract":"<div><p>This minireview explores the burgeoning field of targeted protein degradation (TPD) and its promising applications in neuroscience and clinical development. TPD offers innovative strategies for modulating protein levels, presenting a paradigm shift in small-molecule drug discovery and therapeutic interventions. Importantly, small-molecule protein degraders specifically target and remove pathogenic proteins from central nervous system cells without the drug delivery challenges of genomic and antibody-based modalities. Here, we review recent advancements in TPD technologies, highlight proteolysis targeting chimera (PROTAC) protein degrader molecules with proximity-induced degradation event-driven and iterative pharmacology, provide applications in neuroscience research, and discuss the high potential for translation of TPD into clinical settings.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1688-1698"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003593/pdfft?md5=1f027e9528aca8082bec51fd76809e7f&pid=1-s2.0-S2451945624003593-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Celebrating 30 years of chemical biology: A toast to multidisciplinarity 庆祝化学生物学 30 周年：为多学科性干杯
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.016
Mishtu Dey, Samantha Nelson
{"title":"Celebrating 30 years of chemical biology: A toast to multidisciplinarity","authors":"Mishtu Dey,&nbsp;Samantha Nelson","doi":"10.1016/j.chembiol.2024.08.016","DOIUrl":"10.1016/j.chembiol.2024.08.016","url":null,"abstract":"","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1555-1556"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Insights into bacterial metabolism from small RNAs 从小规模 RNA 了解细菌的新陈代谢
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.07.002
Kai Papenfort , Gisela Storz
{"title":"Insights into bacterial metabolism from small RNAs","authors":"Kai Papenfort ,&nbsp;Gisela Storz","doi":"10.1016/j.chembiol.2024.07.002","DOIUrl":"10.1016/j.chembiol.2024.07.002","url":null,"abstract":"<div><p>The study of small, regulatory RNAs (sRNA) that act by base-pairing with target RNAs in bacteria has been steadily advancing, particularly with the availability of more and more transcriptome and RNA-RNA interactome datasets. While the characterization of multiple sRNAs has helped to elucidate their mechanisms of action, these studies also are providing insights into protein function, control of metabolic flux, and connections between metabolic pathways as we will discuss here. In describing several examples of the metabolic insights gained, we will summarize the different types of base-pairing sRNAs including mRNA-derived sRNAs, sponge RNAs, RNA mimics, and dual-function RNAs as well as suggest how information about sRNAs could be exploited in the future.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1571-1577"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Meet the authors: Lydia P. Tsamouri and Daniel A. Bachovchin 与作者见面：莉迪亚-P-查穆里和丹尼尔-A-巴乔夫钦
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.012
Lydia P. Tsamouri, Daniel A. Bachovchin
{"title":"Meet the authors: Lydia P. Tsamouri and Daniel A. Bachovchin","authors":"Lydia P. Tsamouri,&nbsp;Daniel A. Bachovchin","doi":"10.1016/j.chembiol.2024.08.012","DOIUrl":"10.1016/j.chembiol.2024.08.012","url":null,"abstract":"<div><p>In an interview with Dr. Mishtu Dey, editor-in-chief of <em>Cell Chemical Biology</em>, the authors of the article entitled “The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation” share their perspectives on the ways chemical biology enriches immunology research, the challenges and opportunities in the field, and their scientific career paths.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1568-1570"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003611/pdfft?md5=399618023e792f8827f726e2f978ec23&pid=1-s2.0-S2451945624003611-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Membrane remodeling via ubiquitin-mediated pathways 通过泛素介导的途径重塑细胞膜
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.007
Anne-Claire Jacomin , Ivan Dikic
{"title":"Membrane remodeling via ubiquitin-mediated pathways","authors":"Anne-Claire Jacomin ,&nbsp;Ivan Dikic","doi":"10.1016/j.chembiol.2024.08.007","DOIUrl":"10.1016/j.chembiol.2024.08.007","url":null,"abstract":"<div><p>The dynamic process of membrane shaping and remodeling plays a vital role in cellular functions, with proteins and cellular membranes interacting intricately to adapt to various cellular needs and environmental cues. Ubiquitination—a posttranslational modification—was shown to be essential in regulating membrane structure and shape. It influences virtually all pathways relying on cellular membranes, such as endocytosis and autophagy by directing protein degradation, sorting, and oligomerization. Ubiquitin is mostly known as a protein modifier; however, it was reported that ubiquitin and ubiquitin-like proteins can associate directly with lipids, affecting membrane curvature and dynamics. In this review, we summarize some of the current knowledge on ubiquitin-mediated membrane remodeling in the context of endocytosis, autophagy, and ER-phagy.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1627-1635"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003568/pdfft?md5=ece0af39be652dce7a41d4b687f8ec63&pid=1-s2.0-S2451945624003568-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation CARD8 N 端疏水性可调节炎症小体的激活
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.06.004
{"title":"The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation","authors":"","doi":"10.1016/j.chembiol.2024.06.004","DOIUrl":"10.1016/j.chembiol.2024.06.004","url":null,"abstract":"<div><p><span>Mounting evidence indicates that proteotoxic stress is a primary activator of the CARD8 inflammasome<span>, but the complete array of signals that control this inflammasome<span> have not yet been established. Notably, we recently discovered that several hydrophobic radical-trapping antioxidants (RTAs), including JSH-23, potentiate CARD8 inflammasome<span> activation through an unknown mechanism. Here, we report that these RTAs directly alkylate several cysteine residues in the N-terminal disordered region of CARD8. These hydrophobic modifications destabilize the repressive CARD8 N-terminal fragment and accelerate its proteasome-mediated degradation, thereby releasing the inflammatory CARD8 C-terminal fragment from autoinhibition. Consistently, we also found that unrelated (non-RTA) hydrophobic </span></span></span></span>electrophiles<span><span> as well as genetic mutation<span> of the CARD8 cysteine residues to isoleucines similarly potentiate inflammasome activation. Overall, our results not only provide further evidence that </span></span>protein folding stress is a key CARD8 inflammasome-activating signal, but also indicate that the N-terminal cysteines can play key roles in tuning the response to this stress.</span></p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1699-1713.e8"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets 混合烷基/芳基膦酸盐将代谢丝氨酸水解酶确定为抗疟靶标
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.07.006
John M. Bennett , Sunil K. Narwal , Stephanie Kabeche , Daniel Abegg , Vandana Thathy , Fiona Hackett , Tomas Yeo , Veronica L. Li , Ryan Muir , Franco Faucher , Scott Lovell , Michael J. Blackman , Alexander Adibekian , Ellen Yeh , David A. Fidock , Matthew Bogyo
{"title":"Mixed alkyl/aryl phosphonates identify metabolic serine hydrolases as antimalarial targets","authors":"John M. Bennett ,&nbsp;Sunil K. Narwal ,&nbsp;Stephanie Kabeche ,&nbsp;Daniel Abegg ,&nbsp;Vandana Thathy ,&nbsp;Fiona Hackett ,&nbsp;Tomas Yeo ,&nbsp;Veronica L. Li ,&nbsp;Ryan Muir ,&nbsp;Franco Faucher ,&nbsp;Scott Lovell ,&nbsp;Michael J. Blackman ,&nbsp;Alexander Adibekian ,&nbsp;Ellen Yeh ,&nbsp;David A. Fidock ,&nbsp;Matthew Bogyo","doi":"10.1016/j.chembiol.2024.07.006","DOIUrl":"10.1016/j.chembiol.2024.07.006","url":null,"abstract":"<div><p>Malaria, caused by <em>Plasmodium falciparum,</em> remains a significant health burden. One major barrier for developing antimalarial drugs is the ability of the parasite to rapidly generate resistance. We previously demonstrated that salinipostin A (SalA), a natural product, potently kills parasites by inhibiting multiple lipid metabolizing serine hydrolases, a mechanism that results in a low propensity for resistance. Given the difficulty of employing natural products as therapeutic agents, we synthesized a small library of lipidic mixed alkyl/aryl phosphonates as bioisosteres of SalA. Two constitutional isomers exhibited divergent antiparasitic potencies that enabled the identification of therapeutically relevant targets. The active compound kills parasites through a mechanism that is distinct from both SalA and the pan-lipase inhibitor orlistat and shows synergistic killing with orlistat. Our compound induces only weak resistance, attributable to mutations in a single protein involved in multidrug resistance. These data suggest that mixed alkyl/aryl phosphonates are promising, synthetically tractable antimalarials.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1714-1728.e10"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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