Advances in protein chemistry and structural biology最新文献_第8页

Unlocking estrogen receptor: Structural insights into agonists and antagonists for glioblastoma therapy. 揭开雌激素受体的神秘面纱：从结构上洞察治疗胶质母细胞瘤的激动剂和拮抗剂。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2024-01-01 Epub Date: 2024-07-06 DOI: 10.1016/bs.apcsb.2024.06.001

Asokan Madeshwaran, Periyasamy Vijayalakshmi, Vidhya Rekha Umapathy, Rajeshkumar Shanmugam, Chandrabose Selvaraj

{"title":"Unlocking estrogen receptor: Structural insights into agonists and antagonists for glioblastoma therapy.","authors":"Asokan Madeshwaran, Periyasamy Vijayalakshmi, Vidhya Rekha Umapathy, Rajeshkumar Shanmugam, Chandrabose Selvaraj","doi":"10.1016/bs.apcsb.2024.06.001","DOIUrl":"10.1016/bs.apcsb.2024.06.001","url":null,"abstract":"Glioblastoma (GBM), a malignant brain tumor originating in glial cells, is one of the most common primary brain malignancies, affecting one in 100,000 people, typically in the frontal lobe. Estrogens, like estradiol-17 (E2), significantly influence GBM progression, metastasis, and angiogenesis. Estrogen receptors (ERs) are crucial in signal transduction and physiology, making them potential therapeutic targets. However, their roles in GBM pathogenesis remain unclear. This review explores ERs in GBM, focusing on their involvement in tumor immune evasion, modulation of the tumor microenvironment, and the mechanisms underlying GBM progression. Additionally, therapeutic opportunities targeting ERs for GBM treatment are discussed. Estrogen, synthesized primarily in ovaries and in smaller amounts by adrenal glands and fat tissues, regulates reproductive systems, bone density, skin health, and cardiovascular function. The invasive nature and heterogeneity of GBM complicate therapy development. Preclinical findings suggest that endocrine therapy with hormone receptor agonists or antagonists can extend patient survival and improve post-treatment quality of life. The ERβ pathway, in particular, shows tumor-suppressive potential, limiting glioma progression with fewer side effects. ERβ agonists could become a novel drug class for GBM treatment. Identifying biomarkers and specific therapeutic targets is crucial for early detection and improved prognosis. Estrogen and its receptors are advantageous for GBM treatment due to their regulation of numerous biological processes, ability to penetrate the blood-brain barrier, and genomic and non-genomic control of transcription, making them promising targets for GBM therapy.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764737","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}

引用次数: 0

Cellular signals integrate cell cycle and metabolic control in cancer. 细胞信号整合了肿瘤细胞周期和代谢控制。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2023.01.002

Chareeporn Akekawatchai, Sarawut Jitrapakdee

{"title":"Cellular signals integrate cell cycle and metabolic control in cancer.","authors":"Chareeporn Akekawatchai, Sarawut Jitrapakdee","doi":"10.1016/bs.apcsb.2023.01.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.01.002","url":null,"abstract":"Growth factors are the small peptides that can promote growth, differentiation, and survival of most living cells. However, aberrant activation of receptor tyrosine kinases by GFs can generate oncogenic signals, resulting in oncogenic transformation. Accumulating evidence support a link between GF/RTK signaling through the major signaling pathways, Ras/Erk and PI3K/Akt, and cell cycle progression. In response to GF signaling, the quiescent cells in the G0 stage can re-enter the cell cycle and become the proliferative stage. While in the proliferative stage, tumor cells undergo profound changes in their metabolism to support biomass production and bioenergetic requirements. Accumulating data show that the cell cycle regulators, specifically cyclin D, cyclin B, Cdk2, Cdk4, and Cdk6, and anaphase-promoting complex/cyclosome (APC/C-Cdh1) play critical roles in modulating various metabolic pathways. These cell cycle regulators can regulate metabolic enzyme activities through post-translational mechanisms or the transcriptional factors that control the expression of the metabolic genes. This fine-tune control allows only the relevant metabolic pathways to be active in a particular phase of the cell cycle, thereby providing suitable amounts of biosynthetic precursors available during the proliferative stage. The imbalance of metabolites in each cell cycle phase can induce cell cycle arrest followed by p53-induced apoptosis.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9337448","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}

引用次数: 0

Computational screening and structural analysis of Gly201Arg and Gly201Asp missense mutations in human cyclin-dependent kinase 4 protein. 人周期蛋白依赖性激酶4蛋白Gly201Arg和Gly201Asp错义突变的计算筛选和结构分析。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2023.02.002

D Thirumal Kumar, Nishaat Shaikh, R Bithia, V Karthick, C George Priya Doss, R Magesh

{"title":"Computational screening and structural analysis of Gly201Arg and Gly201Asp missense mutations in human cyclin-dependent kinase 4 protein.","authors":"D Thirumal Kumar, Nishaat Shaikh, R Bithia, V Karthick, C George Priya Doss, R Magesh","doi":"10.1016/bs.apcsb.2023.02.002","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.02.002","url":null,"abstract":"The regulatory proteins, cyclins, and cyclin-dependent kinases (CDKs) control the cell cycle progression. CDK4 gene mutations are associated with certain cancers such as melanoma, breast cancer, and rhabdomyosarcoma. Therefore, understanding the mechanisms of cell cycle control and cell proliferation is essential in developing cancer treatment regimens. In this study, we obtained cancer-causing CDK4 mutations from the COSMIC database and subjected them to a series of in silico analyses to identify the most significant mutations. An overall of 238 mutations (119 missense mutations) retrieved from the COSMIC database were investigated for the pathogenic and destabilizing properties using the PredictSNP and iStable algorithms. Further, the amino acid position of the most pathogenic and destabilizing mutations were analyzed to understand the nature of amino acid conservation across the species during the evolution. We observed that the missense mutations G201R and G201D were more significant and the Glycine at position 201 was found to highly conserved. These significant mutations were subjected to molecular dynamics simulation analysis to understand the protein's structural changes. The results from molecular dynamics simulations revealed that both G201R and G201D of CDK4 are capable of altering the protein's native form. On comparison among the most significant mutations, G201R disrupted the protein structure higher than the protein with G201D.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9337450","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}

引用次数: 0

Targeting mitochondrial dysfunction to salvage cellular senescence for managing neurodegeneration. 靶向线粒体功能障碍挽救细胞衰老以治疗神经退行性疾病。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2023.02.016

Komal Sharma, Joyobrata Sarkar, Anchal Trisal, Rishika Ghosh, Anubhuti Dixit, Abhishek Kumar Singh

{"title":"Targeting mitochondrial dysfunction to salvage cellular senescence for managing neurodegeneration.","authors":"Komal Sharma, Joyobrata Sarkar, Anchal Trisal, Rishika Ghosh, Anubhuti Dixit, Abhishek Kumar Singh","doi":"10.1016/bs.apcsb.2023.02.016","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.02.016","url":null,"abstract":"Aging is an inevitable phenomenon that causes a decline in bodily functions over time. One of the most important processes that play a role in aging is senescence. Senescence is characterized by accumulation of cells that are no longer functional but elude the apoptotic pathway. These cells secrete inflammatory molecules that comprise the senescence associated secretory phenotype (SASP). Several essential molecules such as p53, Rb, and p16INK4a regulate the senescence process. Mitochondrial regulation has been found to play an important role in senescence. Reactive oxygen species (ROS) generated from mitochondria can affect cellular senescence by inducing the persistent DNA damage response, thus stabilizing the senescence. Evidently, senescence plays a major contributory role to the development of age-related neurological disorders. In this chapter, we discuss the role of senescence in the progression and onset of several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Moreover, we also discuss the efficacy of certain molecules like MitoQ, SkQ1, and Latrepirdine that could be proven therapeutics with respect to these disorders by regulating mitochondrial activity.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239511","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}

引用次数: 0

Molecular characterization of circadian gene expression and its correlation with survival percentage in colorectal cancer patients. 癌症患者昼夜节律基因表达的分子特征及其与生存率的相关性。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 Epub Date: 2023-03-01 DOI: 10.1016/bs.apcsb.2023.02.007

Ankur Datta, Hephzibah Cathryn R, S Udhaya Kumar, Karthick Vasudevan, D Thirumal Kumar, Hatem Zayed, C George Priya Doss

{"title":"Molecular characterization of circadian gene expression and its correlation with survival percentage in colorectal cancer patients.","authors":"Ankur Datta, Hephzibah Cathryn R, S Udhaya Kumar, Karthick Vasudevan, D Thirumal Kumar, Hatem Zayed, C George Priya Doss","doi":"10.1016/bs.apcsb.2023.02.007","DOIUrl":"10.1016/bs.apcsb.2023.02.007","url":null,"abstract":"Colorectal cancer (CRC) is a form of cancer characterized by many symptoms and readily metastasizes to different organs in the body. Circadian rhythm is one of the many processes that is observed to be dysregulated in CRC-affected patients. In this study, we aim to identify the dysregulated physiological processes in CRC-affected patients and correlate the expression profiles of the circadian clock genes with CRC-patients' survival rates. We performed an extensive microarray gene expression pipeline, whereby 471 differentially expressed genes (DEGs) were identified, following which, we streamlined our search to 43 circadian clock affecting DEGs. The Circadian Gene Database was accessed to retrieve the circadian rhythm-specific genes. The DEGs were then subjected to multi-level functional annotation, i.e., preliminary analysis using ClueGO/CluePedia and pathway enrichment using DAVID. The findings of our study were interesting, wherein we observed that the survival percentage of CRC-affected patients dropped significantly around the 100th-month mark. Furthermore, we identified hormonal activity, xenobiotic metabolism, and PI3K-Akt signaling pathway to be frequently dysregulated cellular functions. Additionally, we detected that the ZFYVE family of genes and the two genes, namely MYC and CDK4 were the significant DEGs that are linked to the pathogenesis and progression of CRC. This study sheds light on the importance of bioinformatics to simplify our understanding of the interactions of different genes that control different phenotypes.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287727","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}

引用次数: 0

Mitochondria-derived peptides in healthy ageing and therapy of age-related diseases. 线粒体衍生肽在健康衰老和年龄相关疾病的治疗中的作用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2023.02.015

Siarhei A Dabravolski

引用次数: 0

Importin alpha family NAAT/IBB domain: Functions of a pleiotropic long chameleon sequence. 导入α家族NAAT/IBB结构域:多向长变色龙序列的功能。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2022.11.005

Kazuya Jibiki, Takashi S Kodama, Noriko Yasuhara

{"title":"Importin alpha family NAAT/IBB domain: Functions of a pleiotropic long chameleon sequence.","authors":"Kazuya Jibiki, Takashi S Kodama, Noriko Yasuhara","doi":"10.1016/bs.apcsb.2022.11.005","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.11.005","url":null,"abstract":"Nuclear transport is essential for eukaryotic cell survival and regulates the movement of functional molecules in and out of the nucleus via the nuclear pore. Transport is facilitated by protein-protein interactions between cargo and transport receptors, which contribute to the expression and regulation of downstream genetic information. This chapter focuses on the molecular basis of the multifunctional nature of the importin α family, the representative transport receptors that bring proteins into the nucleus. Importin α performs multiple functions during the nuclear transport cycle through interactions with multiple molecules by a single domain called the IBB domain. This domain is a long chameleon sequence, which can change its conformation and binding mode depending on the interaction partners. By considering the evolutionarily conserved biochemical/physicochemical propensities of the amino acids constituting the functional complex interfaces, together with their structural properties, the mechanisms of switching between multiple complexes formed via IBB and the regulation of downstream functions are examined in detail. The mechanism of regulation by IBB indicates that the time has come for a paradigm shift in the way we view the molecular mechanisms by which proteins regulate downstream functions through their interactions with other molecules.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335419","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}

引用次数: 0

CDK regulators-Cell cycle progression or apoptosis-Scenarios in normal cells and cancerous cells. CDK调节因子-细胞周期进展或凋亡-正常细胞和癌细胞的情况。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2022.11.008

Nilmani, Maria D'costa, Anusha Bothe, Soumik Das, S Udhaya Kumar, R Gnanasambandan, C George Priya Doss

{"title":"CDK regulators-Cell cycle progression or apoptosis-Scenarios in normal cells and cancerous cells.","authors":"Nilmani, Maria D'costa, Anusha Bothe, Soumik Das, S Udhaya Kumar, R Gnanasambandan, C George Priya Doss","doi":"10.1016/bs.apcsb.2022.11.008","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.11.008","url":null,"abstract":"Serine/threonine kinases called cyclin-dependent kinases (CDKs) interact with cyclins and CDK inhibitors (CKIs) to control the catalytic activity. CDKs are essential controllers of RNA transcription and cell cycle advancement. The ubiquitous overactivity of the cell cycle CDKs is caused by a number of genetic and epigenetic processes in human cancer, and their suppression can result in both cell cycle arrest and apoptosis. This review focused on CDKs, describing their kinase activity, their role in phosphorylation inhibition, and CDK inhibitory proteins (CIP/KIP, INK 4, RPIC). We next compared the role of different CDKs, mainly p21, p27, p57, p16, p15, p18, and p19, in the cell cycle and apoptosis in cancer cells with respect to normal cells. The current work also draws attention to the use of CDKIs as therapeutics, overcoming the pharmacokinetic barriers of pan-CDK inhibitors, analyze new chemical classes that are effective at attacking the CDKs that control the cell cycle (cdk4/6 or cdk2). It also discusses CDKI's drawbacks and its combination therapy against cancer patients. These findings collectively demonstrate the complexity of cancer cell cycles and the need for targeted therapeutic intervention. In order to slow the progression of the disease or enhance clinical outcomes, new medicines may be discovered by researching the relationship between cell death and cell proliferation.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9344133","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}

引用次数: 3

Therapeutic targets in cancer treatment: Cell cycle proteins. 癌症治疗的治疗靶点:细胞周期蛋白。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2023.02.003

Chandrabose Selvaraj

引用次数: 1

Proprotein convertases regulate trafficking and maturation of key proteins within the secretory pathway. 蛋白转化酶调节分泌通路中关键蛋白的转运和成熟。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2023-01-01 DOI: 10.1016/bs.apcsb.2022.10.001

Laura Cendron, Sylvia Rothenberger, Leonardo Cassari, Monica Dettin, Antonella Pasquato

{"title":"Proprotein convertases regulate trafficking and maturation of key proteins within the secretory pathway.","authors":"Laura Cendron, Sylvia Rothenberger, Leonardo Cassari, Monica Dettin, Antonella Pasquato","doi":"10.1016/bs.apcsb.2022.10.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.10.001","url":null,"abstract":"Proprotein Convertases (PCs) are serine endoproteases that regulate the homeostasis of protein substrates in the cell. The PCs family counts 9 members-PC1/3, PC2, PC4, PACE4, PC5/6, PC7, Furin, SKI-1/S1P, and PCSK9. The first seven PCs are known as Basic Proprotein Convertases due to their propensity to cleave after polybasic clusters. SKI-1/S1P requires the additional presence of hydrophobic residues for processing, whereas PCSK9 is catalytically dead after autoactivation and exerts its functions using mechanisms alternative to direct cleavage. All PCs traffic through the canonical secretory pathway, reaching different compartments where the various substrates reside. Despite PCs members do not share the same subcellular localization, most of the cellular organelles count one or more Proprotein Convertases, including ER, Golgi stack, endosomes, secretory granules, and plasma membranes. The widespread expression of these enzymes at the systemic level speaks for their importance in the homeostasis of a large number of biological functions. Among others, PCs cleave precursors of hormones and growth factors and activate receptors and transcription factors. Notably, dysregulation of the enzymatic activity of Proprotein Convertases is associated to major human pathologies, such as cardiovascular diseases, cancer, diabetes, infections, inflammation, autoimmunity diseases, and Parkinson. In the current COVID-19 pandemic, Furin has further attracted the attention as a key player for conferring high pathogenicity to SARS-CoV-2. Here, we review the Proprotein Convertases family and their most important substrates along the secretory pathway. Knowledge about the complex functions of PCs is important to identify potential drug strategies targeting this class of enzymes.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10632701","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}

引用次数: 1