Advances in protein chemistry and structural biology最新文献

{"title":"Evolution of biosynthetic human insulin and its analogues for diabetes management.","authors":"Dileep Francis, Aksa Mariyam Chacko, Anagha Anoop, Subramani Nadimuthu, Vaishnavi Venugopal","doi":"10.1016/bs.apcsb.2024.06.004","DOIUrl":"10.1016/bs.apcsb.2024.06.004","url":null,"abstract":"<p><p>Hormones play a crucial role in maintaining the normal human physiology. By acting as chemical messengers that facilitate the communication between different organs, tissues and cells of the body hormones assist in responding appropriately to external and internal stimuli that trigger growth, development and metabolic activities of the body. Any abnormalities in the hormonal composition and balance can lead to devastating health consequences. Hormones have been important therapeutic agents since the early 20th century, when it was realized that their exogenous supply could serve as a functional substitution for those hormones which are not produced enough or are completely lacking, endogenously. Insulin, the pivotal anabolic hormone in the body, was used for the treatment of diabetes mellitus, a metabolic disorder due to the absence or intolerance towards insulin, since 1921 and is the trailblazer in hormone therapeutics. At present the largest market share for therapeutic hormones is held by insulin. Many other hormones were introduced into clinical practice following the success with insulin. However, for the six decades following the introduction the first therapeutic hormone, there was no reliable method for producing human hormones. The most common source for hormones were animals, although semisynthetic and synthetic hormones were also developed. However, none of these were optimal because of their allergenicity, immunogenicity, lack of consistency in purity and most importantly, scalability. The advent of recombinant DNA technology was a game changer for hormone therapeutics. This revolutionary molecular biology tool made it possible to synthesize human hormones in microbial cell factories. The approach allowed for the synthesis of highly pure hormones which were structurally and biochemically identical to the human hormones. Further, the fermentation techniques utilized to produce recombinant hormones were highly scalable. Moreover, by employing tools such as site directed mutagenesis along with recombinant DNA technology, it became possible to amend the molecular structure of the hormones to achieve better efficacy and mimic the exact physiology of the endogenous hormone. The first recombinant hormone to be deployed in clinical practice was insulin. It was called biosynthetic human insulin to reflect the biological route of production. Subsequently, the biochemistry of recombinant insulin was modified using the possibilities of recombinant DNA technology and genetic engineering to produce analogues that better mimic physiological insulin. These analogues were tailored to exhibit pharmacokinetic and pharmacodynamic properties of the prandial and basal human insulins to achieve better glycemic control. The present chapter explores the principles of genetic engineering applied to therapeutic hormones by reviewing the evolution of therapeutic insulin and its analogues. It also focuses on how recombinant analogues account for the better","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"142 ","pages":"191-256"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic dysregulation in cancers by isocitrate dehydrogenase 2 (IDH2).","authors":"Anuraj Nayarisseri, Srinivas Bandaru, Arshiya Khan, Khushboo Sharma, Anushka Bhrdwaj, Manmeet Kaur, Dipannita Ghosh, Ishita Chopra, Aravind Panicker, Abhishek Kumar, Priyadevi Saravanan, Pranoti Belapurkar, Francisco Jaime Bezerra Mendonça Junior, Sanjeev Kumar Singh","doi":"10.1016/bs.apcsb.2023.12.012","DOIUrl":"10.1016/bs.apcsb.2023.12.012","url":null,"abstract":"<p><p>Recent advances in genome-wide studies have revealed numerous epigenetic regulations brought about by genes involved in cellular metabolism. Isocitrate dehydrogenase (IDH), an essential enzyme, that converts isocitrate into -ketoglutarate (KG) predominantly in the tricarboxylic acid (TCA) cycle, has gained particular importance due to its cardinal role in the metabolic pathway in cells. IDH1, IDH2, and IDH3 are the three isomeric IDH enzymes that have been shown to regulate cellular metabolism. Of particular importance, IDH2 genes are associated with several cancers, including gliomas, oligodendroglioma, and astrocytomas. These mutations lead to the production of oncometabolite D-2-hydroxyglutarate (D-2-HG), which accumulates in cells promoting tumor growth. The enhanced levels of D-2-HG competitively inhibit α-KG dependent enzymes, inhibiting cell TCA cycle, upregulating the cell growth and survival relevant HIF-1α pathway, promoting DNA hypermethylation related epigenetic activity, all of which synergistically contribute to carcinogenesis. The present review discusses epigenetic mechanisms inIDH2 regulation in cells and further its clinical implications.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"223-253"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications.","authors":"Cícero Alves Lopes Júnior, Mikael Kélvin de Albuquerque Mendes, Michely da Silva Sousa, Edivan Carvalho Vieira, Tatianny de Araujo Andrade, Jemmyson Romário de Jesus","doi":"10.1016/bs.apcsb.2024.03.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.03.002","url":null,"abstract":"<p><p>Several species during evolution suffered random mutations in response to various environmental factors, which resulted in the formation of venom in phylogenetically distant species. The composition of the venom of most species is poorly known. Snake venom is well characterized while most species have poorly known composition. In contrast, snake venoms are well characterized which proteins and peptides are the main active and most abundant constituents. 42 protein families have been identified, including metalloproteins known as metalloproteinases. These macromolecules are enzymes with zinc in their active site derived from the disintegrin A and metalloproteinase (ADAM) cellular family and are categorized into three classes (PI, PII and PIII) according to their domain organization. The snake venom metalloproteinases (SVMP) are cytotoxic, neurotoxic, myotoxic and/or hematotoxic with a crucial role in the defense and restraint of prey. In this scenario envenoming represents a danger to human health and has been considered a neglected disease worldwide, particularly in tropical and subtropical countries. Nevertheless, recently advances in \"omics\" technologies have demonstrated interesting biological activities of SVMPs such as antimicrobial, anticancer, against cardiovascular diseases and nervous system disorders. Metalloproteins have the therapeutic potential to be converted into drugs as other components of the venom have undergone this process (e.g., captopril, tirefiban and eptifibatide). So, this chapter is focused on the metalloproteins found in the secretions of venomous species, highlight some aspects such as structure, biological activity, pharmacological therapeutic potential and on.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"539-562"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-protein coupled receptors regulates Tauopathy in neurodegeneration.","authors":"Subashchandrabose Chinnathambi, Hariharakrishnan Chidambaram","doi":"10.1016/bs.apcsb.2024.04.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.04.001","url":null,"abstract":"<p><p>In Alzheimer's disease, the microtubule-associated protein, Tau misfolds to form aggregates and filaments in the intra- and extracellular region of neuronal cells. Microglial cells are the resident brain macrophage cells involved in constant surveillance and activated by the extracellular deposits. Purinergic receptors are involved in the chemotactic migration of microglial cells towards the site of inflammation. From our recent study, we have observed that the microglial P2Y12 receptor is involved in phagocytosis of full-length Tau species such as monomers, oligomers and aggregates by actin-driven chemotaxis. This study shows the interaction of repeat-domain of Tau (Tau^RD) with the microglial P2Y12 receptor and the corresponding residues for interaction have been analyzed by various in-silico approaches. In the cellular studies, Tau^RD was found to interact with microglial P2Y12R and induces its cellular expression confirmed by co-immunoprecipitation and western blot analysis. Furthermore, the P2Y12R-mediated Tau^RD internalization has demonstrated activation of microglia with an increase in the Iba1 level, and Tau^RD becomes accumulated at the peri-nuclear region for the degradation.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"467-493"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular insights and promise of oncolytic virus based immunotherapy.","authors":"Mahalaxmi Iyer, Nandita Ravichandran, Panimalar Abirami Karuppusamy, Roselin Gnanarajan, Mukesh Kumar Yadav, Arul Narayanasamy, Balachandar Vellingiri","doi":"10.1016/bs.apcsb.2023.12.007","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.007","url":null,"abstract":"<p><p>Discovering a therapeutic that can counteract the aggressiveness of this disease's mechanism is crucial for improving survival rates for cancer patients and for better understanding the most different types of cancer. In recent years, using these viruses as an anticancer therapy has been thought to be successful. They mostly work by directly destroying cancer cells, activating the immune system to fight cancer, and expressing exogenous effector genes. For the treatment of tumors, oncolytic viruses (OVs), which can be modified to reproduce only in tumor tissues and lyse them while preserving the healthy non-neoplastic host cells and reinstating antitumor immunity which present a novel immunotherapeutic strategy. OVs can exist naturally or be created in a lab by altering existing viruses. These changes heralded the beginning of a new era of less harmful virus-based cancer therapy. We discuss three different types of oncolytic viruses that have already received regulatory approval to treat cancer as well as clinical research using oncolytic adenoviruses. The primary therapeutic applications, mechanism of action of oncolytic virus updates, future views of this therapy will be covered in this chapter.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"419-492"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pattern recognition receptors as potential therapeutic targets for developing immunological engineered plants.","authors":"Deeksha Singh, Shivangi Mathur, Rajiv Ranjan","doi":"10.1016/bs.apcsb.2024.02.006","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.02.006","url":null,"abstract":"<p><p>There is an urgent need to combat pathogen infestations in crop plants to ensure food security worldwide. To counter this, plants have developed innate immunity mediated by Pattern Recognition Receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and damage- associated molecular patterns (DAMPs). PRRs activate Pattern-Triggered Immunity (PTI), a defence mechanism involving intricate cell-surface and intracellular receptors. The diverse ligand-binding ectodomains of PRRs, including leucine-rich repeats (LRRs) and lectin domains, facilitate the recognition of MAMPs and DAMPs. Pathogen resistance is mediated by a variety of PTI responses, including membrane depolarization, ROS production, and the induction of defence genes. An integral part of intracellular immunity is the Nucleotide-binding Oligomerization Domain, Leucine-rich Repeat proteins (NLRs) which recognize and respond to effectors in a potent manner. Enhanced understanding of PRRs, their ligands, and downstream signalling pathways has contributed to the identification of potential targets for genetically modified plants. By transferring PRRs across plant species, it is possible to create broad-spectrum resistance, potentially offering innovative solutions for plant protection and global food security. The purpose of this chapter is to provide an update on PRRs involved in disease resistance, clarify the mechanisms by which PRRs recognize ligands to form active receptor complexes and present various applications of PRRs and PTI in disease resistance management for plants.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"525-555"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding macrophage immunometabolism in human viral infection.","authors":"Takhellambam Malemnganba, Aditi Rattan, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2023.12.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.003","url":null,"abstract":"<p><p>Immune-metabolic interactions play a pivotal role in both host defense and susceptibility to various diseases. Immunometabolism, an interdisciplinary field, seeks to elucidate how metabolic processes impact the immune system. In the context of viral infections, macrophages are often exploited by viruses for their replication and propagation. These infections trigger significant metabolic reprogramming within macrophages and polarization of distinct M1 and M2 phenotypes. This metabolic reprogramming involves alterations in standard- pathways such as the Krebs cycle, glycolysis, lipid metabolism, the pentose phosphate pathway, and amino acid metabolism. Disruptions in the balance of key intermediates like spermidine, itaconate, and citrate within these pathways contribute to the severity of viral diseases. In this chapter, we describe the manipulation of metabolic pathways by viruses and how they crosstalk between signaling pathways to evade the immune system. This intricate interplay often involves the upregulation or downregulation of specific metabolites, making these molecules potential biomarkers for diseases like HIV, HCV, and SARS-CoV. Techniques such as Nuclear Magnetic Resonance (NMR) and Mass Spectrometry, are the evaluative ways to analyze these metabolites. Considering the importance of macrophages in the inflammatory response, addressing their metabolome holds great promise for the creating future therapeutic targets aimed at combating a wide spectrum of viral infections.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"493-523"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-based solutions for managing mucormycosis.","authors":"Ritu Tomer, Sumeet Patiyal, Dilraj Kaur, Shubham Choudhury, Gajendra P S Raghava","doi":"10.1016/bs.apcsb.2023.11.014","DOIUrl":"10.1016/bs.apcsb.2023.11.014","url":null,"abstract":"<p><p>An uncommon opportunistic fungal infection known as mucormycosis is caused by a class of molds called mucoromycetes. Currently, antifungal therapy and surgical debridement are the primary treatment options for mucormycosis. Despite the importance of comprehensive knowledge on mucormycosis, there is a lack of well-annotated databases that provide all relevant information. In this study, we have gathered and organized all available information related to mucormycosis that include disease's genome, proteins, diagnostic methods. Furthermore, using the AlphaFold2.0 prediction tool, we have predicted the tertiary structures of potential drug targets. We have categorized the information into three major sections: \"genomics/proteomics,\" \"immunotherapy,\" and \"drugs.\" The genomics/proteomics module contains information on different strains responsible for mucormycosis. The immunotherapy module includes putative sequence-based therapeutics predicted using established tools. Drugs module provides information on available drugs for treating the disease. Additionally, the drugs module also offers prerequisite information for designing computationally aided drugs, such as putative targets and predicted structures. In order to provide comprehensive information over internet, we developed a web-based platform MucormyDB (https://webs.iiitd.edu.in/raghava/mucormydb/).</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"139 ","pages":"383-403"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140048545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered CAR-T cells: An immunotherapeutic approach for cancer treatment and beyond.","authors":"Purva Khodke, Bajarang Vasant Kumbhar","doi":"10.1016/bs.apcsb.2023.12.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.12.001","url":null,"abstract":"<p><p>Chimeric Antigen Receptor (CAR) T cell therapy is a type of adoptive immunotherapy that offers a promising avenue for enhancing cancer treatment since traditional cancer treatments like chemotherapy, surgery, and radiation therapy have proven insufficient in completely eradicating tumors, despite the relatively positive outcomes. It has been observed that CAR-T cell therapy has shown promising results in treating the majority of hematological malignancies but also have a wide scope for other cancer types. CAR is an extra receptor on the T-cell that helps to increase and accelerate tumor destruction by efficiently activating the immune system. It is made up of three domains, the ectodomain, transmembrane, and the endodomain. The ectodomain is essential for antigen recognition and binding, whereas the co-stimulatory signal is transduced by the endodomain. To date, the Food and Drug Administration (FDA) has granted approval for six CAR-T cell therapies. However, despite its remarkable success, CAR-T therapy is associated with numerous adverse events and has certain limitations. This chapter focuses on the structure and function of the CAR domain, various generations of CAR, and the process of CAR-T cell development, adverse effects, and challenges in CAR-T therapy. CAR-T cell therapy also has scopes in other disease conditions which include systemic lupus erythematosus, multiple sclerosis, and myocardial fibrosis, etc.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"140 ","pages":"157-198"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140955639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metalloproteins structural and functional insights into immunological patterns.","authors":"Chandrabose Selvaraj, Periyasamy Vijayalakshmi, Asha Monica Alex, Abdulaziz S Alothaim, Rajendran Vijayakumar, Vidhya Rekha Umapathy","doi":"10.1016/bs.apcsb.2024.03.009","DOIUrl":"10.1016/bs.apcsb.2024.03.009","url":null,"abstract":"<p><p>Metalloproteins play a crucial role in regulating different aspects of the immune system in humans. They have various functions in immunity, including recognizing and presenting antigens, aiding in the movement and effectiveness of immune cells, and facilitating interactions between the host and pathogens. Understanding how these proteins work can help us develop new methods to control the immune response in different diseases. Metalloproteins contain metal ions in their structure, which allows them to perform these diverse functions. They encompass a wide range of enzymes, signaling molecules, and structural proteins that utilize metal ions as cofactors for their activities. Examples of metalloproteins include superoxide dismutase, catalase, and metalloproteases, which regulate oxidative stress, inflammation, and tissue remodelling processes associated with immune activation. By studying their functions and the effects of their dysfunction, researchers can develop strategies to improve immune function and combat various diseases. This review explores the diverse functions of metalloproteins in immune processes, highlighting their significance in both health and disease.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"141 ","pages":"67-86"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}