Pub Date : 2024-06-10DOI: 10.1038/s41557-024-01552-7
Bang Wang, James R. Rocca, Shuichi Hoshika, Cen Chen, Zunyi Yang, Reza Esmaeeli, Jianguo Wang, Xiaoshu Pan, Jianrong Lu, Kevin K. Wang, Y. Charles Cao, Weihong Tan, Steven A. Benner
Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ−:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ−:dZ pairs join parallel strands in a four-stranded compact down–up–down–up fold. These have two possible structures: one with intercalated dZ−:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC+-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.
在 DNA 中添加合成核苷酸可以增加 DNA 分子的线性信息密度。我们在这里报告说，它还能增加其三维折叠的多样性。具体地说，在 23 个核苷酸长的 DNA 链的 12 个位点上添加一个核苷酸（dZ，含有一个 5-硝基-6-氨基吡啶酮核碱基），就能形成一个相当稳定的单分子结构（即折叠 Z-motif，或 fZ-motif），在 pH 值为 8.5 时熔点为 66.5 °C。光谱、凝胶和二维核磁共振分析表明，折叠 Z-motif由六个反向瘦dZ-:dZ碱基对固定在一起，类似于游离杂环的晶体结构。荧光标记显示，dZ-:dZ 对以四股紧凑的下-上-下-上折叠方式连接平行链。这种结构有两种可能：一种是 dZ-:dZ 碱基对插层结构，另一种是无插层结构。夹层结构类似于 pH ≤ 6.5 时 dC:dC+ 反向配对形成的 i-motif。因此，这种 fZ 标记可能有助于 DNA 形成结合和催化所需的紧凑结构。
{"title":"A folding motif formed with an expanded genetic alphabet","authors":"Bang Wang, James R. Rocca, Shuichi Hoshika, Cen Chen, Zunyi Yang, Reza Esmaeeli, Jianguo Wang, Xiaoshu Pan, Jianrong Lu, Kevin K. Wang, Y. Charles Cao, Weihong Tan, Steven A. Benner","doi":"10.1038/s41557-024-01552-7","DOIUrl":"https://doi.org/10.1038/s41557-024-01552-7","url":null,"abstract":"<p>Adding synthetic nucleotides to DNA increases the linear information density of DNA molecules. Here we report that it also can increase the diversity of their three-dimensional folds. Specifically, an additional nucleotide (dZ, with a 5-nitro-6-aminopyridone nucleobase), placed at twelve sites in a 23-nucleotides-long DNA strand, creates a fairly stable unimolecular structure (that is, the folded Z-motif, or fZ-motif) that melts at 66.5 °C at pH 8.5. Spectroscopic, gel and two-dimensional NMR analyses show that the folded Z-motif is held together by six reverse skinny dZ<sup>−</sup>:dZ base pairs, analogous to the crystal structure of the free heterocycle. Fluorescence tagging shows that the dZ<sup>−</sup>:dZ pairs join parallel strands in a four-stranded compact down–up–down–up fold. These have two possible structures: one with intercalated dZ<sup>−</sup>:dZ base pairs, the second without intercalation. The intercalated structure would resemble the i-motif formed by dC:dC<sup>+</sup>-reversed pairing at pH ≤ 6.5. This fZ-motif may therefore help DNA form compact structures needed for binding and catalysis.</p><figure></figure>","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-10DOI: 10.1038/s41557-024-01549-2
Jiratheep Pruchyathamkorn, Bao-Nguyen T. Nguyen, Angela B. Grommet, Miroslava Novoveska, Tanya K. Ronson, John D. Thoburn, Jonathan R. Nitschke
Maxwell’s demon describes a thought experiment in which a ‘demon’ regulates the flow of particles between two adjoining spaces, establishing a potential gradient without appearing to do work. This seeming paradox led to the understanding that sorting entails thermodynamic work, a foundational concept of information theory. In the past centuries, many systems analogous to Maxwell’s demon have been introduced in the form of molecular information, molecular pumps and ratchets. Here we report a functional example of a Maxwell’s demon that pumps material over centimetres, whereas previous examples operated on a molecular scale. In our system, this demon drives directional transport of o-fluoroazobenzene between the arms of a U-tube apparatus upon light irradiation, transiting through an aqueous membrane containing a coordination cage. The concentration gradient thus obtained is further harnessed to drive naphthalene transport in the opposite direction. In the original Maxwell’s demon thought experiment, a potential gradient of particles between two neighbouring compartments is created without the apparent use of work. Now a functional example of this experiment where material is pumped over centimetres has been reported—o-fluoroazobenzene is transported unidirectionally under light stimulation between two arms of a U-tube across an aqueous layer containing coordination cages.
麦克斯韦的恶魔 "描述了一个思想实验，在这个实验中，一个 "恶魔 "调节两个相邻空间之间的粒子流，建立了一个电势梯度，但似乎并没有做功。这个看似矛盾的现象让人们认识到，排序需要热力学功，这是信息论的一个基础概念。在过去的几个世纪中，人们以分子信息、分子泵和棘轮的形式提出了许多与麦克斯韦妖类似的系统。在这里，我们报告了一个麦克斯韦恶魔的功能实例，它能将材料泵送到几厘米的范围内，而之前的实例是在分子尺度上运行的。在我们的系统中，当光线照射时，麦克斯韦妖驱动邻氟偶氮苯在 U 形管装置的两臂之间定向传输，并通过含有配位笼的水膜。由此获得的浓度梯度被进一步用于驱动萘的反向传输。
{"title":"Harnessing Maxwell’s demon to establish a macroscale concentration gradient","authors":"Jiratheep Pruchyathamkorn, Bao-Nguyen T. Nguyen, Angela B. Grommet, Miroslava Novoveska, Tanya K. Ronson, John D. Thoburn, Jonathan R. Nitschke","doi":"10.1038/s41557-024-01549-2","DOIUrl":"10.1038/s41557-024-01549-2","url":null,"abstract":"Maxwell’s demon describes a thought experiment in which a ‘demon’ regulates the flow of particles between two adjoining spaces, establishing a potential gradient without appearing to do work. This seeming paradox led to the understanding that sorting entails thermodynamic work, a foundational concept of information theory. In the past centuries, many systems analogous to Maxwell’s demon have been introduced in the form of molecular information, molecular pumps and ratchets. Here we report a functional example of a Maxwell’s demon that pumps material over centimetres, whereas previous examples operated on a molecular scale. In our system, this demon drives directional transport of o-fluoroazobenzene between the arms of a U-tube apparatus upon light irradiation, transiting through an aqueous membrane containing a coordination cage. The concentration gradient thus obtained is further harnessed to drive naphthalene transport in the opposite direction. In the original Maxwell’s demon thought experiment, a potential gradient of particles between two neighbouring compartments is created without the apparent use of work. Now a functional example of this experiment where material is pumped over centimetres has been reported—o-fluoroazobenzene is transported unidirectionally under light stimulation between two arms of a U-tube across an aqueous layer containing coordination cages.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41557-024-01549-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141299086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1038/s41557-024-01540-x
Zhuojia Xu, Yating Liu, Jialin Liu, Wenjing Ma, Zhumin Zhang, Digantkumar G. Chapla, Liuqing Wen, Kelley W. Moremen, Wen Yi, Tiehai Li
Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein–carbohydrate interactions. Structural and functional insights into the biological roles of these glycans are impeded due to the limited accessibility of well-defined structures. Here we report an integrated chemoenzymatic strategy for expeditious and systematic synthesis of a comprehensive 65-membered ganglioside glycan library covering all possible patterns of sulfation and sialylation. This strategy relies on the streamlined modular assembly of three common sialylated precursors by highly stereoselective iterative sialylation, modular site-specific sulfation through flexible orthogonal protecting-group manipulations and enzymatic-catalysed diversification using three sialyltransferase modules and a galactosidase module. These diverse ganglioside glycans enable exploration into their structure–function relationships using high-throughput glycan microarray technology, which reveals that different patterns of sulfation and sialylation on these glycans mediate their unique binding specificities. Deciphering the sulfation and sialylation codes of ganglioside glycans is impeded by the limited accessibility of well-defined structures. Now, an integrated chemoenzymatic strategy has been developed for efficient synthesis of a comprehensive 65-membered ganglioside glycan library, enabling an extensive exploration into their structure–function relationships using glycan microarray technology.
{"title":"Integrated chemoenzymatic synthesis of a comprehensive sulfated ganglioside glycan library to decipher functional sulfoglycomics and sialoglycomics","authors":"Zhuojia Xu, Yating Liu, Jialin Liu, Wenjing Ma, Zhumin Zhang, Digantkumar G. Chapla, Liuqing Wen, Kelley W. Moremen, Wen Yi, Tiehai Li","doi":"10.1038/s41557-024-01540-x","DOIUrl":"10.1038/s41557-024-01540-x","url":null,"abstract":"Ganglioside glycans are ubiquitous and complex biomolecules that are involved in a wide range of biological functions and disease processes. Variations in sialylation and sulfation render the structural complexity and diversity of ganglioside glycans, and influence protein–carbohydrate interactions. Structural and functional insights into the biological roles of these glycans are impeded due to the limited accessibility of well-defined structures. Here we report an integrated chemoenzymatic strategy for expeditious and systematic synthesis of a comprehensive 65-membered ganglioside glycan library covering all possible patterns of sulfation and sialylation. This strategy relies on the streamlined modular assembly of three common sialylated precursors by highly stereoselective iterative sialylation, modular site-specific sulfation through flexible orthogonal protecting-group manipulations and enzymatic-catalysed diversification using three sialyltransferase modules and a galactosidase module. These diverse ganglioside glycans enable exploration into their structure–function relationships using high-throughput glycan microarray technology, which reveals that different patterns of sulfation and sialylation on these glycans mediate their unique binding specificities. Deciphering the sulfation and sialylation codes of ganglioside glycans is impeded by the limited accessibility of well-defined structures. Now, an integrated chemoenzymatic strategy has been developed for efficient synthesis of a comprehensive 65-membered ganglioside glycan library, enabling an extensive exploration into their structure–function relationships using glycan microarray technology.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1038/s41557-024-01543-8
Sabine L. Flitsch, Josef Voglmeir
By employing chemo-enzymatic techniques, a diverse 65-member ganglioside glycan library has been generated that provides a comprehensive insight into ganglioside-mediated cellular communication.
{"title":"Chemo-enzymatic synthesis is spot on for ganglioside glycan libraries","authors":"Sabine L. Flitsch, Josef Voglmeir","doi":"10.1038/s41557-024-01543-8","DOIUrl":"10.1038/s41557-024-01543-8","url":null,"abstract":"By employing chemo-enzymatic techniques, a diverse 65-member ganglioside glycan library has been generated that provides a comprehensive insight into ganglioside-mediated cellular communication.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1038/s41557-024-01544-7
Madeleine B. King, Kayla N. Perry, Mitchell J. McAndrew, Audrone Lapinaite
In molecular biology, few molecules have had as profound an impact as Cas9. Madeleine King, Kayla Perry, Mitchell McAndrew and Audrone Lapinaite discuss how this multifunctional molecular tool of genetic engineering is revolutionizing multiple fields.
{"title":"The genetic engineering Swiss army knife","authors":"Madeleine B. King, Kayla N. Perry, Mitchell J. McAndrew, Audrone Lapinaite","doi":"10.1038/s41557-024-01544-7","DOIUrl":"10.1038/s41557-024-01544-7","url":null,"abstract":"In molecular biology, few molecules have had as profound an impact as Cas9. Madeleine King, Kayla Perry, Mitchell McAndrew and Audrone Lapinaite discuss how this multifunctional molecular tool of genetic engineering is revolutionizing multiple fields.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-06DOI: 10.1038/s41557-024-01551-8
Heng Liu, Ding-Wei Ji, Yong-Kang Mei, Yan Liu, Chang-Hui Liu, Xiao-Yu Wang, Qing-An Chen
Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs. The presence of halogens in halogenated organic pollutants has negative impacts on the environment; however, they serve as valuable sources for halogenation reactions. Now it has been shown that transfer chlorination reactions enable the repurposing of halogenated organic pollutants for the synthesis of chlorides and bromides.
{"title":"Repurposing of halogenated organic pollutants via alkyl bromide-catalysed transfer chlorination","authors":"Heng Liu, Ding-Wei Ji, Yong-Kang Mei, Yan Liu, Chang-Hui Liu, Xiao-Yu Wang, Qing-An Chen","doi":"10.1038/s41557-024-01551-8","DOIUrl":"10.1038/s41557-024-01551-8","url":null,"abstract":"Halogenated organic pollutants (HOPs) are causing a significant environmental and human health crisis due to their high levels of toxicity, persistence and bioaccumulation. Urgent action is required to develop effective approaches for the reduction and reuse of HOPs. Whereas current strategies focus primarily on the degradation of HOPs, repurposing them is an alternative approach, albeit a challenging task. Here we discover that alkyl bromide can act as a catalyst for the transfer of chlorine using alkyl chloride as the chlorine source. We demonstrate that this approach has a wide substrate scope, and we successfully apply it to reuse HOPs that include dichlorodiphenyltrichloroethane, hexabromocyclododecane, chlorinated paraffins, chloromethyl polystyrene and poly(vinyl chloride) (PVC). Moreover, we show that the synthesis of essential non-steroidal anti-inflammatory drugs can be achieved using PVC and hexabromocyclododecane, and we demonstrate that PVC waste can be used directly as a chlorinating agent. Overall, this methodology offers a promising strategy for repurposing HOPs. The presence of halogens in halogenated organic pollutants has negative impacts on the environment; however, they serve as valuable sources for halogenation reactions. Now it has been shown that transfer chlorination reactions enable the repurposing of halogenated organic pollutants for the synthesis of chlorides and bromides.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141264798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-05DOI: 10.1038/s41557-024-01554-5
Shira Joudan
Environmental contamination is in the news more than ever. Shira Joudan introduces key concepts to talk about what happens to chemicals in the environment and what chemists should consider in their day-to-day lives, both at work and at home.
{"title":"How we talk about harmful chemicals in the environment","authors":"Shira Joudan","doi":"10.1038/s41557-024-01554-5","DOIUrl":"10.1038/s41557-024-01554-5","url":null,"abstract":"Environmental contamination is in the news more than ever. Shira Joudan introduces key concepts to talk about what happens to chemicals in the environment and what chemists should consider in their day-to-day lives, both at work and at home.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-04DOI: 10.1038/s41557-024-01545-6
Yansheng Zhai, Xinyu Zhang, Zijing Chen, Dingyuan Yan, Lin Zhu, Zhe Zhang, Xianghe Wang, Kailu Tian, Yan Huang, Xi Yang, Wen Sun, Dong Wang, Yu-Hsuan Tsai, Tuoping Luo, Gang Li
Recent advances in chemical proteomics have focused on developing chemical probes that react with nucleophilic amino acid residues. Although histidine is an attractive candidate due to its importance in enzymatic catalysis, metal binding and protein–protein interaction, its moderate nucleophilicity poses challenges. Its modification is frequently influenced by cysteine and lysine, which results in poor selectivity and narrow proteome coverage. Here we report a singlet oxygen and chemical probe relay labelling method that achieves high selectivity towards histidine. Libraries of small-molecule photosensitizers and chemical probes were screened to optimize histidine labelling, enabling histidine profiling in live cells with around 7,200 unique sites. Using NMR spectroscopy and X-ray crystallography, we characterized the reaction mechanism and the structures of the resulting products. We then applied this method to discover unannotated histidine sites key to enzymatic activity and metal binding in select metalloproteins. This method also revealed the accessibility change of histidine mediated by protein–protein interaction that influences select protein subcellular localization, underscoring its capability in discovering functional histidines. Chemical probes that selectively react with histidine could afford functional insight for those located in vital protein regions, but the moderate nucleophilicity of histidine and interference from other residues pose challenges. A singlet oxygen and chemical probe relay labelling approach demonstrates high selectivity, enabling comprehensive histidine profiling and providing crucial functional insights.
化学蛋白质组学的最新进展主要集中在开发能与亲核氨基酸残基发生反应的化学探针上。虽然组氨酸在酶催化、金属结合和蛋白质-蛋白质相互作用中具有重要作用，因此是一种有吸引力的候选物质，但其适度的亲核性也带来了挑战。组氨酸的修饰经常受到半胱氨酸和赖氨酸的影响，从而导致选择性差和蛋白质组覆盖范围窄。在此，我们报告了一种单线态氧和化学探针接力标记方法，该方法对组氨酸具有高选择性。我们筛选了小分子光敏剂和化学探针库，以优化组氨酸标记，从而实现了活细胞中约 7,200 个独特位点的组氨酸分析。利用核磁共振光谱和 X 射线晶体学，我们确定了反应机制和生成物的结构。然后，我们应用这种方法发现了未注明的组氨酸位点，这些位点是酶活性和金属结合的关键。该方法还揭示了组氨酸在蛋白质与蛋白质相互作用过程中发生的可及性变化，这种变化影响了特定蛋白质的亚细胞定位，从而凸显了该方法在发现功能组氨酸方面的能力。
{"title":"Global profiling of functional histidines in live cells using small-molecule photosensitizer and chemical probe relay labelling","authors":"Yansheng Zhai, Xinyu Zhang, Zijing Chen, Dingyuan Yan, Lin Zhu, Zhe Zhang, Xianghe Wang, Kailu Tian, Yan Huang, Xi Yang, Wen Sun, Dong Wang, Yu-Hsuan Tsai, Tuoping Luo, Gang Li","doi":"10.1038/s41557-024-01545-6","DOIUrl":"10.1038/s41557-024-01545-6","url":null,"abstract":"Recent advances in chemical proteomics have focused on developing chemical probes that react with nucleophilic amino acid residues. Although histidine is an attractive candidate due to its importance in enzymatic catalysis, metal binding and protein–protein interaction, its moderate nucleophilicity poses challenges. Its modification is frequently influenced by cysteine and lysine, which results in poor selectivity and narrow proteome coverage. Here we report a singlet oxygen and chemical probe relay labelling method that achieves high selectivity towards histidine. Libraries of small-molecule photosensitizers and chemical probes were screened to optimize histidine labelling, enabling histidine profiling in live cells with around 7,200 unique sites. Using NMR spectroscopy and X-ray crystallography, we characterized the reaction mechanism and the structures of the resulting products. We then applied this method to discover unannotated histidine sites key to enzymatic activity and metal binding in select metalloproteins. This method also revealed the accessibility change of histidine mediated by protein–protein interaction that influences select protein subcellular localization, underscoring its capability in discovering functional histidines. Chemical probes that selectively react with histidine could afford functional insight for those located in vital protein regions, but the moderate nucleophilicity of histidine and interference from other residues pose challenges. A singlet oxygen and chemical probe relay labelling approach demonstrates high selectivity, enabling comprehensive histidine profiling and providing crucial functional insights.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":19.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141246558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-03DOI: 10.1038/s41557-024-01536-7
Daniela Danková, Christian A. Olsen
Posttranslational modifications alter the structure and function of proteins. Now, genetic code expansion enables encoding of ε-N-succinyllysine and ε-N-glutaryllysine residues to decipher the effects of these modifications on enzymatic activity, protein–protein interactions and protein–DNA interactions.
{"title":"Reversing the charge of lysine by genetic code expansion","authors":"Daniela Danková, Christian A. Olsen","doi":"10.1038/s41557-024-01536-7","DOIUrl":"10.1038/s41557-024-01536-7","url":null,"abstract":"Posttranslational modifications alter the structure and function of proteins. Now, genetic code expansion enables encoding of ε-N-succinyllysine and ε-N-glutaryllysine residues to decipher the effects of these modifications on enzymatic activity, protein–protein interactions and protein–DNA interactions.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141235944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-30DOI: 10.1038/s41557-024-01538-5
Quanbin Dai, Liming Dai
Ethylene feedstocks must be ultrapure for plastics production, but metal-based catalysts used for acetylene removal are limited by cost, scarcity and durability. Now, electrochemical studies demonstrate that 2-thiolimidazole exceeds the efficiency of traditional metal-based catalysts with remarkable selectivity and conversion rates.
{"title":"Metal-free catalysts for hydrogenation","authors":"Quanbin Dai, Liming Dai","doi":"10.1038/s41557-024-01538-5","DOIUrl":"10.1038/s41557-024-01538-5","url":null,"abstract":"Ethylene feedstocks must be ultrapure for plastics production, but metal-based catalysts used for acetylene removal are limited by cost, scarcity and durability. Now, electrochemical studies demonstrate that 2-thiolimidazole exceeds the efficiency of traditional metal-based catalysts with remarkable selectivity and conversion rates.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":null,"pages":null},"PeriodicalIF":21.8,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141177222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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