Sub-cellular biochemistry最新文献_第2页

Regulation of Glycan Modification by Glycosyltransferases in the Golgi Apparatus. 高尔基体中糖基转移酶对聚糖修饰的调控。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-16833-7_11

Hirokazu Yagi, Seigo Tateo, Koichi Kato

{"title":"Regulation of Glycan Modification by Glycosyltransferases in the Golgi Apparatus.","authors":"Hirokazu Yagi, Seigo Tateo, Koichi Kato","doi":"10.1007/978-3-032-16833-7_11","DOIUrl":"https://doi.org/10.1007/978-3-032-16833-7_11","url":null,"abstract":"Protein glycosylation, a fundamental modification critical for diverse biological functions, is well orchestrated within the Golgi apparatus, a central organelle in the secretory pathway. This review explores the mechanisms by which the Golgi governs protein-specific glycan modification, emphasizing the spatial organization of glycosyltransferases within the Golgi and the regulated transport of glycoproteins through its compartments. Specificity arises from the strategic localization of glycosyltransferases within the Golgi, enabling them to recognize both glycan structures and protein domains on their substrates. Advanced imaging reveals a complex and dynamic organization within the Golgi, challenging traditional models and highlighting specialized zones. Regulated transport of glycoproteins through the Golgi is critical for controlling their access to modifying enzymes. Specific sequence motifs within glycoproteins can act as 'passport sequence', directing them to distinct Golgi regions and influencing glycosylation by altering their proximity to specific enzymes and accessory proteins. These mechanisms support the hypothesis that sequence-dependent signals within substrate proteins influence their trafficking, enabling precise glycosylation as they transit the Golgi. Understanding these processes provides new insights into how glycan diversity is generated and regulated within the Golgi, highlighting the interplay between enzyme localization, protein trafficking, and the dynamic organization of this essential organelle.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"251-267"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Microtubule Nucleation at the Golgi Apparatus. 高尔基体微管成核研究。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-16833-7_12

Rosa M Rios, María P Gavilán

{"title":"Insights into Microtubule Nucleation at the Golgi Apparatus.","authors":"Rosa M Rios, María P Gavilán","doi":"10.1007/978-3-032-16833-7_12","DOIUrl":"https://doi.org/10.1007/978-3-032-16833-7_12","url":null,"abstract":"The arrangement of microtubule (MT) networks is essential for various cellular processes including chromosome segregation during cell division, organelle positioning and transport, and the maintenance of cell polarity and morphology. The configuration of MT arrays heavily depends on the sites of MT assembly and anchoring of their minus ends. These sites are often organized into specialized structures known as microtubule-organizing centers (MTOCs). The nucleation activity of MTOCs relies on MT-nucleating factors, such as γ-tubulin-containing complexes, their associated activators and receptors, and proteins that anchor and stabilize MT minus ends.Traditionally, the centrosome has been considered the primary MTOC in animal cells. However, recent research has revealed significant contributions from other subcellular structures in shaping MT networks. Notably, the Golgi Apparatus (GA) has emerged as a prominent alternative MTOC, operating in a diverse range of organisms from Drosophila to humans and across various cell types, from undifferentiated cells to highly specialized ones. This novel activity expands the functional repertoire of the GA, complementing its central role in secretion with essential contributions to MT cytoskeleton configuration.This chapter offers a comprehensive overview of the current understanding of MT formation at the GA, including how this process is coordinated with the centrosome. It also explores the specific functions of Golgi-nucleated MTs and their participation in generating the complex MT networks of specialized cells, such as neurons, muscle cells, and pancreatic cells.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"111 ","pages":"271-315"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug Design of Carbonic Anhydrase Inhibitors. 碳酸酐酶抑制剂的药物设计。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-23172-7_3

Neera Raghav, Niccolò Paoletti, Claudiu T Supuran

{"title":"Drug Design of Carbonic Anhydrase Inhibitors.","authors":"Neera Raghav, Niccolò Paoletti, Claudiu T Supuran","doi":"10.1007/978-3-032-23172-7_3","DOIUrl":"https://doi.org/10.1007/978-3-032-23172-7_3","url":null,"abstract":"Carbonic anhydrases (CAs) are ubiquitous zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide and play essential roles in numerous physiological and pathological processes. Over the past decades, carbonic anhydrase inhibitors (CAIs) have emerged as valuable therapeutic agents for the treatment of a variety of human disorders, including glaucoma, epilepsy, altitude sickness, and, more recently, cancer and infectious diseases. This chapter provides a comprehensive overview of the principles and strategies underlying the rational design and synthesis of CA inhibitors. The two fundamental medicinal chemistry approaches for CAI development, the \"ring approach\" and the \"tail approach,\" are discussed in detail, emphasizing the versatility and effectiveness of these strategies in optimizing binding affinity and enhancing isoform selectivity. Both classical zinc-binding inhibitors, such as sulfonamides and related chemotypes, and nonclassical inhibitors acting through alternative mechanisms are discussed. Among nonclassical inhibitors, particular attention is devoted to natural product-derived scaffolds, such as coumarins and polyamines, which have gained considerable interest due to their selective inhibition of the tumor-associated isoforms hCA IX/hCA XII, and hCA IV, respectively. The chapter also evaluates the increasing number of recently reported nonclassical chemotypes for which X-ray crystal structures in adduct with the enzymes are however not available. Finally, an overview of the main synthetic methodologies employed for the preparation of the different classes of CA inhibitors is presented, providing practical insights into the chemical strategies most commonly used in this field.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"29-57"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Epigenetic Angle in the Precision Medicine Era for Blood Disorder Advancements. 精准医学时代血液疾病进展的表观遗传学角度。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-08530-6_6

Nadia M Hamdy, Ahmed I Abulsoud, Nehal I Rizk, Tohada M Al-Noshokaty, Mohamed Bakr Zaki, Ahmed S Sultan, Ahmed S Doghish

{"title":"The Epigenetic Angle in the Precision Medicine Era for Blood Disorder Advancements.","authors":"Nadia M Hamdy, Ahmed I Abulsoud, Nehal I Rizk, Tohada M Al-Noshokaty, Mohamed Bakr Zaki, Ahmed S Sultan, Ahmed S Doghish","doi":"10.1007/978-3-032-08530-6_6","DOIUrl":"10.1007/978-3-032-08530-6_6","url":null,"abstract":"This work examined the integration of epigenetics and precision medicine in the management of various blood disorders, including anemias, antiphospholipid syndrome, hemochromatosis, hemophilia, leukemia, lymphoma, multiple myeloma, porphyria, thalassemia, thrombocytopenia, thrombocytosis, polycythemia, von Willebrand disease, and coagulopathy. It begins with an overview of key concepts and the significance of precision medicine in treating blood diseases, supported by current statistics. The role of noncoding RNAs (ncRNAs) is highlighted, detailing their mechanisms of action and clinical implications as potential biomarkers and therapeutic targets. Additionally, the chapter explores natural products used in personalized medicine, examining their sources, mechanisms, and successful case studies in blood disorders. A comprehensive review of recent clinical trials provides insights into the impact of innovative therapies and FDA approvals on treatment protocols, emphasizing the importance of combination therapies. Future directions address emerging research technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) and ethical considerations surrounding genetic testing and patient consent. The synthesis of findings underscores the contributions of epigenetics and precision medicine to blood disease treatment, advocating for interdisciplinary research and ongoing education to enhance patient care and outcomes.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"114 ","pages":"299-353"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure of the Myosin Thick Filaments in Muscle. 肌球蛋白粗丝的结构。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-05273-5_2

Pradeep K Luther

{"title":"Structure of the Myosin Thick Filaments in Muscle.","authors":"Pradeep K Luther","doi":"10.1007/978-3-032-05273-5_2","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_2","url":null,"abstract":"Striated muscle is composed of overlapping arrays of thick myosin filaments and thin actin filaments. The thick filaments are composed of myosin molecules, which are hexamers of two heavy chains and two pairs of light chains. The heavy chain has an N-terminal head domain and a C-terminal helical rod domain. The latter dimerises to form a two-stranded coiled-coil rod. The distal two-thirds of these rods aggregate in parallel to form the filament backbone, while the heads lie on the surface to facilitate interactions with actin. The molecules aggregate in an antiparallel manner in the centre of the A-band to form the so-called bare zone. The proximal one-third of the rod can swivel and thereby allow the myosin heads to interact with actin. The atomic structure of the head, determined in the 1990s, was a major milestone in the muscle field. Over the next three decades, great strides were made in cryo-electron microscope technology and software. This led to the high-resolution structure of the insect flight muscle thick filament, showing the structure of the myosin tails at 6 Å resolution and the structure of the heads. There has been great excitement recently with the high-resolution structures of relaxed cardiac muscle thick filaments showing details of all the important players: three types of myosin crowns and the paths of their tails, the structure and interactions of cMyBP-C and the structure of two unique forms of titin and its role in filament assembly. Hypertrophic cardiomyopathy, which results from mutations in sarcomeric proteins, especially myosin and cMyBP-C, is a major health burden and insight gained from the new studies will help to devise new therapies.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"35-58"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and Functional Elements of the Epidermal Appendages in Birds and Reptiles: Conformations and Modes of Assembly of the Constituent β-Filaments and Keratin Intermediate Filaments (IF). 鸟类和爬行动物表皮附属物的结构和功能要素：组成β-丝和角蛋白中间丝（IF）的构象和组装模式。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-05273-5_5

David A D Parry

{"title":"Structural and Functional Elements of the Epidermal Appendages in Birds and Reptiles: Conformations and Modes of Assembly of the Constituent β-Filaments and Keratin Intermediate Filaments (IF).","authors":"David A D Parry","doi":"10.1007/978-3-032-05273-5_5","DOIUrl":"10.1007/978-3-032-05273-5_5","url":null,"abstract":"Much is now known about the structures of the β-filaments and the intermediate filaments that together constitute the bulk of the avian and reptilian (sauropsid) appendages (claws, scales, feathers and beaks). New sequence data from the Rhynchocephalia (the tuatara), the last branch of the phylogenetic classification of the sauropsids to be studied, has confirmed that all members of the sauropsids are based on common structures. In addition, an examination of the sequence data has revealed that the β-filaments in the lepidosaurs (lizards, snakes and tuatara) contain a chain that is likely to be a structural component of two separate filaments, thereby providing a unique feature that could facilitate ordered filament aggregation. Similarly, a Type II IF chain (K80) in lizards appears capable of forming an interaction in inter-filament space that would link adjacent IF through tail-tail interactions. A Type II IF chain in zebra finch (K78LT) also seems likely to play a similar role. More details of the surface lattice structure in the IF have also been obtained, as has information on the lateral packing of the protofilaments in the IF. Consequently, an increasingly detailed picture has emerged of the structure and assembly of the filamentous structures that comprise the corneous appendages in the sauropsids.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"113-142"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

COG Complex in Golgi Trafficking and Glycosylation. 高尔基转运和糖基化中的COG复合物。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-16833-7_7

Farhana Taher Sumya, Vladimir V Lupashin

引用次数: 0

Carbonic Anhydrase Inhibitors in Oncology. 肿瘤中的碳酸酐酶抑制剂。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-23172-7_6

Claudiu T Supuran, Andrea Angeli

{"title":"Carbonic Anhydrase Inhibitors in Oncology.","authors":"Claudiu T Supuran, Andrea Angeli","doi":"10.1007/978-3-032-23172-7_6","DOIUrl":"https://doi.org/10.1007/978-3-032-23172-7_6","url":null,"abstract":"Tumor hypoxia and extracellular acidosis are hallmarks of the tumor microenvironment that promote cancer progression, metabolic adaptation, and resistance to therapy. Among the molecular mediators of these processes, carbonic anhydrase IX (CA IX) and carbonic anhydrase XII (CA XII) play central roles in maintaining intracellular pH homeostasis and facilitating tumor cell survival under hypoxic stress, making them highly attractive targets for selective therapeutic intervention. This has prompted an effort to inhibit specific CA isoforms, as an anticancer therapeutic strategy with small molecule inhibitors, one of which (SLC-0111) completed Phase I clinical trials. However, other CA isoforms also show similar activity and tissue distribution in cancers and have not been considered as therapeutic targets for cancer treatment. Recent findings have revealed that CA IX and CA XII are not only critical for pH regulation but also intersect with key metabolic and redox pathways, including ferroptosis, glutathione metabolism, and mitochondrial iron-sulfur cluster biogenesis. Parallel advances in drug design have expanded this therapeutic paradigm through the development of dual-target inhibitors, combining CA IX/XII inhibition with modulation of other cancer-associated pathways. Beyond small-molecule inhibitors, antibody-based approaches have reached clinical and preclinical development as imaging agents, radioimmunotherapeutics, antibody-drug conjugates, and nanomaterial conjugates. Collectively, these strategies highlight the potential of exploiting the metabolic vulnerabilities of hypoxic tumors by co-targeting CA IX/XII with complementary redox or survival pathways, paving the way toward rational polypharmacology in precision oncology.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"101-146"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Industrial and Environmental Applications of Carbonic Anhydrases. 碳酸酐酶的工业和环境应用。

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-23172-7_9

Claudiu T Supuran, Rashmi Pundeer, Clemente Capasso

{"title":"Industrial and Environmental Applications of Carbonic Anhydrases.","authors":"Claudiu T Supuran, Rashmi Pundeer, Clemente Capasso","doi":"10.1007/978-3-032-23172-7_9","DOIUrl":"https://doi.org/10.1007/978-3-032-23172-7_9","url":null,"abstract":"Carbonic anhydrases (CAs) are highly efficient metalloenzymes catalyzing the reversible conversion of carbon dioxide (CO2) into bicarbonate (HCO3-) and protons (H+). Over the past decades, CAs have been employed across diverse industrial and environmental applications, including carbon management and CO2 capture, chemical synthesis, biomineralization, water treatment, and renewable energy generation. This chapter provides a comprehensive overview of CA-based technologies, emphasizing their transition from laboratory research to pilot- and industrial-scale applications. Key topics covered include enzyme-assisted CO2 absorption, reactor and solvent design, enzyme immobilization, and hybrid systems integrating chemical, biological, or electrochemical conversion. The chapter also examines operational challenges, mitigation strategies, and future perspectives, highlighting how CAs can enable sustainable, low-energy, and value-added processes. It illustrates the integration of mechanistic insights, process design, and real-world examples, providing a valuable resource for both researchers and industrial practitioners.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"123 ","pages":"179-194"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Collagen in Fibrotic Diseases. 胶原蛋白在纤维化疾病中的作用

Sub-cellular biochemistry Pub Date : 2026-01-01 DOI: 10.1007/978-3-032-05273-5_11

Andrzej Fertala

{"title":"Collagen in Fibrotic Diseases.","authors":"Andrzej Fertala","doi":"10.1007/978-3-032-05273-5_11","DOIUrl":"https://doi.org/10.1007/978-3-032-05273-5_11","url":null,"abstract":"This chapter explores the role of fibrillar collagens, mainly collagen I, in developing fibrotic disorders associated with acute or chronic injuries. While collagen molecules' fundamental structure, composition, and intracellular biosynthesis steps remain similar in healthy and scar tissues, their extracellular architecture and physical properties significantly differ. These differences arise from the excessive production of collagen I and auxiliary proteins associated with collagen I folding and posttranslational modifications. As a result, the overaccumulation of collagen I-based fibrotic deposits creates a rigid mechanical environment that, through mechanotransduction, amplifies pro-fibrotic signaling in resident fibroblasts.In reviewing the literature, this chapter highlights key players that create, transmit, and sustain these signals, thereby perpetuating fibrosis. Given the growing recognition of mechanotransduction as a valid therapeutic target to limit fibrosis, this chapter also discusses strategies to inhibit different elements of this process. A significant challenge with these strategies is that both balanced and excessive scarring rely on the exact underlying mechanisms of scar tissue formation. Consequently, conventional anti-fibrotic agents may inadvertently impair the essential scarring needed to preserve tissue integrity after injury. Therefore, mechanotherapeutics that reduce collagen accumulation-driven scar stiffness represent a novel approach for developing more targeted anti-fibrotic therapies.","PeriodicalId":21991,"journal":{"name":"Sub-cellular biochemistry","volume":"113 ","pages":"343-375"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146012332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0