{"title":"The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control","authors":"Chia-Wei Hu, Ke Wang, Jiaoyang Jiang","doi":"10.1016/j.cbpa.2024.102476","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102476","url":null,"abstract":"<div><p>O-GlcNAcylation is an essential protein glycosylation governed by two O-GlcNAc cycling enzymes: O-GlcNAc transferase (OGT) installs a single sugar moiety <em>N-</em>acetylglucosamine (GlcNAc) on protein serine and threonine residues, and O-GlcNAcase (OGA) removes them. Aberrant O-GlcNAcylation has been implicated in various diseases. However, the large repertoire of more than 1000 O-GlcNAcylated proteins and the elusive mechanisms of OGT/OGA in substrate recognition present significant challenges in targeting the dysregulated O-GlcNAcylation for therapeutic development. Recently, emerging evidence suggested that the non-catalytic domains play critical roles in regulating the functional specificity of OGT/OGA via modulating their protein interactions and substrate recognition. Here, we discuss recent studies on the structures, mechanisms, and related tools of the OGT/OGA non-catalytic domains, highlighting new opportunities for function-specific control.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102476"},"PeriodicalIF":7.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302468","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}
{"title":"Probing metalloenzyme dynamics in living systems: Contemporary advances in fluorescence imaging tools and applications","authors":"Sky Price, Emily L. Que","doi":"10.1016/j.cbpa.2024.102475","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102475","url":null,"abstract":"<div><p>Metalloenzymes are essential to cellular function, and their overexpression or enhanced activation are potential therapeutic targets. However, the study of metalloenzymes <em>in vitro</em> presents various challenges, leading many to develop tools to study them in their native cellular environment. Small-molecule fluorescence probes are commonly used to monitor metalloenzyme function, activity, and distribution <em>in situ</em>. These include probes that are activity-based (fluorescence is mediated by enzyme activity) or binding-based (fluorescence is mediated by interactions with the enzyme upon binding its metal cofactor). We discuss recent innovations that overcome key design challenges, such as the rapid diffusion of activity-based probes, the difficulty of probing redox-active enzymes, the selectivity of binding-based probes, and the poor penetration depth of fluorescence, and describe novel applications of these tools.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102475"},"PeriodicalIF":7.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294167","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}
{"title":"Molecular anchoring and fluorescent labeling in animals compatible with tissue clearing for 3D imaging","authors":"Takeharu Mino , Hiroshi Nonaka , Itaru Hamachi","doi":"10.1016/j.cbpa.2024.102474","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102474","url":null,"abstract":"<div><p>Analyzing the quantity and distribution of molecules throughout intact biological tissue is crucial for understanding various biological phenomena. Traditional methods involving destructive extraction result in the loss of spatial information. Conversely, tissue-clearing techniques combined with fluorescence imaging have recently emerged as a powerful tool for deep tissue imaging without sacrificing spatial coverage. Key to this approach is the anchoring and labeling of targets in intact tissue. In this review, methods for anchoring and labeling proteins, lipids, carbohydrates, and small molecules are presented. Future directions include the development of activity-based probes that work in vivo and mark transient events with spatial information to enable a deeper understanding of biological phenomena.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102474"},"PeriodicalIF":7.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000504/pdfft?md5=36af80453465d5781e5a415a7c90e9f8&pid=1-s2.0-S1367593124000504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251029","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}
Joni Sebastiano , Zachary V. Samuels , Wei-Siang Kao , Brian M. Zeglis
{"title":"Site-specific bioconjugation and nuclear imaging","authors":"Joni Sebastiano , Zachary V. Samuels , Wei-Siang Kao , Brian M. Zeglis","doi":"10.1016/j.cbpa.2024.102471","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102471","url":null,"abstract":"<div><p>Monoclonal antibodies and antibody fragments have proven to be highly effective vectors for the delivery of radionuclides to target tissues for positron emission tomography (PET) and single-photon emission computed tomography (SPECT). However, the stochastic methods that have traditionally been used to attach radioisotopes to these biomolecules inevitably produce poorly defined and heterogeneous probes and can impair the ability of the immunoglobulins to bind their molecular targets. In response to this challenge, an array of innovative site-specific and site-selective bioconjugation strategies have been developed, and these approaches have repeatedly been shown to yield better-defined and more homogeneous radioimmunoconjugates with superior <em>in vivo</em> performance than their randomly modified progenitors. In this <em>Current Opinion in Chemical Biology</em> review, we will examine recent advances in this field, including the development — and, in some cases, clinical translation — of nuclear imaging agents radiolabeled using strategies that target the heavy chain glycans, peptide tags, and unnatural amino acids.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102471"},"PeriodicalIF":7.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000474/pdfft?md5=1845bb97421825784919bf8d45590ec7&pid=1-s2.0-S1367593124000474-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141244761","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}
{"title":"New reactions by pyridoxal phosphate-dependent enzymes","authors":"Phillip Daniel-Ivad, Katherine S. Ryan","doi":"10.1016/j.cbpa.2024.102472","DOIUrl":"10.1016/j.cbpa.2024.102472","url":null,"abstract":"<div><p>Pyridoxal phosphate (PLP) is a cofactor that is widely employed in enzymology. This pyridine-containing cofactor can be used for reactions ranging from transaminations to oxidations. The catalytic versatility can be understood by considering the chemical features of this cofactor. In recent years, exciting new reactions involving PLP have been discovered in natural products biosynthesis, upending our understanding of what this cofactor is capable of. Here we review some of the most exciting PLP-dependent reactions from the last five years.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102472"},"PeriodicalIF":7.8,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000486/pdfft?md5=90c95973227f092b2660e8c5a58d3bd9&pid=1-s2.0-S1367593124000486-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141178450","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}
{"title":"Specific signaling by nicotinamide adenine dinucleotide oxidases – Role of their site of action","authors":"Katrin Schröder","doi":"10.1016/j.cbpa.2024.102461","DOIUrl":"10.1016/j.cbpa.2024.102461","url":null,"abstract":"<div><p>Nicotinamide adenine dinucleotide (NADPH) oxidases, known for their role in generating reactive oxygen species (ROS) have emerged as key regulators of specific cellular signaling pathways. While their primary function is ROS production, recent research has highlighted the significance of their site-specific activity in governing distinct cellular signaling events.</p><p>NADPH oxidases (Nox) are found in various cell types, and both their expression and activities are tightly regulated. The generated ROS, such as superoxide anions and hydrogen peroxide, function as secondary messengers that modulate various signaling molecules, including protein kinases, transcription factors, and phosphatases.</p><p>The site-specific action of NADPH oxidases in different cellular compartments, such as the plasma membrane, endosomes, and endoplasmic reticulum, allows for precise control over specific signaling pathways. Understanding the complex interplay of NADPH oxidases in cellular signaling is essential for deciphering their roles in health and disease. Dysregulation of these enzymes can lead to oxidative stress and inflammation, making them potential therapeutic targets in various pathological conditions. Ongoing research into NADPH oxidase activation and site-specific signaling promises to unveil new insights into cellular physiology and potential treatment strategies.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102461"},"PeriodicalIF":7.8,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173631","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}
Kaimin Jia , Helen Sun , Yiyan Zhou , Wenjun Zhang
{"title":"Biosynthesis of isonitrile lipopeptides","authors":"Kaimin Jia , Helen Sun , Yiyan Zhou , Wenjun Zhang","doi":"10.1016/j.cbpa.2024.102470","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102470","url":null,"abstract":"<div><p>Isonitrile lipopeptides discovered from Actinobacteria have attracted wide attention due to their fascinating biosynthetic pathways and relevance to the virulence of many human pathogens including <em>Mycobacterium tuberculosis</em>. Specifically, the identification of the new class of isonitrile-forming enzymes that belong to non-heme iron (II) and α-ketoglutarate dependent dioxygenases has intrigued several research groups to investigate their catalytic mechanism. Here we summarize the recent studies on the biosynthesis of isonitrile lipopeptides from <em>Streptomyces</em> and <em>Mycobacterium</em>. The latest research on the core and tailoring enzymes involved in the pathway as well as the isonitrile metabolic enzymes are discussed in this review.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102470"},"PeriodicalIF":7.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090176","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}
{"title":"Lanthanide-dye hybrid luminophores for advanced NIR-II bioimaging","authors":"Mei Mei, Bin Wu, Shangfeng Wang, Fan Zhang","doi":"10.1016/j.cbpa.2024.102469","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102469","url":null,"abstract":"<div><p>In vivo luminescence imaging in the second near-infrared window (NIR-II, 1000–2000 nm) is a potent technique for observing deep-tissue life activities, leveraging reduced light scattering, minimized autofluorescence, and moderate absorption attenuation to substantially enhance image contrast. Pushing the frontiers of NIR-II luminescence imaging forward, moving from static to dynamic event visualization, monochromatic to multicolor images, and fundamental research to clinical applications, necessitates the development of novel luminophores featuring bright emission, extendable wavelength, and optimal biocompatibility. Recently, lanthanide-dye hybrid luminophores (LDHLs) are gaining increasing attention for their wavelength extensibility, molecular size, narrowband emission, mega stokes shift, long lifetime, and high photostability. In this review, we will summarize the recent advances of NIR-II LDHLs and their applications in imaging and analysis of living mammals, and discuss future challenges in designing new LDHLs for deep-tissue imaging.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102469"},"PeriodicalIF":7.8,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072927","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}
{"title":"F420-dependent transformations in biosynthesis of secondary metabolites","authors":"Ghader Bashiri","doi":"10.1016/j.cbpa.2024.102468","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102468","url":null,"abstract":"<div><p>Cofactor F<sub>420</sub> has been historically known as the “methanogenic redox cofactor”. It is now recognised that F<sub>420</sub> has essential roles in the primary and secondary metabolism of archaea and bacteria. Recent discoveries highlight the role of F<sub>420</sub> as a redox cofactor in the biosynthesis of various natural products, including ribosomally synthesised and post-translationally modified peptides, and a new class of nicotinamide adenine dinucleotide-based secondary metabolites. With the vast availability of (meta)genomic data, the identification of uncharacterised F<sub>420</sub>-dependent enzymes offers the potential for discovering novel secondary metabolites, presenting valuable prospects for clinical and biotechnological applications.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102468"},"PeriodicalIF":7.8,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000449/pdfft?md5=ecc1a03e1981ca1f49df232c88201ce5&pid=1-s2.0-S1367593124000449-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072926","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}
{"title":"Multinuclear non-heme iron dependent oxidative enzymes (MNIOs) involved in unusual peptide modifications","authors":"Jeff Y. Chen, Wilfred A. van der Donk","doi":"10.1016/j.cbpa.2024.102467","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102467","url":null,"abstract":"<div><p>Multinuclear non-heme iron dependent oxidative enzymes (MNIOs), formerly known as domain of unknown function 692 (DUF692), are involved in the post-translational modification of peptides during the biosynthesis of peptide-based natural products. These enzymes catalyze highly unusual and diverse chemical modifications. Several class-defining features of this large family (>14 000 members) are beginning to emerge. Structurally, the enzymes are characterized by a TIM-barrel fold and a set of conserved residues for a di- or tri–iron binding site. They use molecular oxygen to modify peptide substrates, often in a four-electron oxidation taking place at a cysteine residue. This review summarizes the current understanding of MNIOs. Four modifications are discussed in detail: oxazolone-thioamide formation, β-carbon excision, hydantoin-macrocycle formation, and 5-thiooxazole formation. Briefly discussed are two other reactions that do not take place on Cys residues.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"80 ","pages":"Article 102467"},"PeriodicalIF":7.8,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000437/pdfft?md5=ff0d2067bb16ebe523993dbaeab8b350&pid=1-s2.0-S1367593124000437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072924","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}