Open Biochemistry Journal最新文献_第8页

Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity. 杨梅素抑制胰岛淀粉样多肽(IAPP)聚集并拯救IAPP毒性的活哺乳动物细胞。

Open Biochemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-06-27 DOI: 10.2174/1874091X01206010066

Casey Zelus, Ayano Fox, Anastasia Calciano, Bianca S Faridian, Luiza A Nogaj, David A Moffet

{"title":"Myricetin Inhibits Islet Amyloid Polypeptide (IAPP) Aggregation and Rescues Living Mammalian Cells from IAPP Toxicity.","authors":"Casey Zelus, Ayano Fox, Anastasia Calciano, Bianca S Faridian, Luiza A Nogaj, David A Moffet","doi":"10.2174/1874091X01206010066","DOIUrl":"https://doi.org/10.2174/1874091X01206010066","url":null,"abstract":"The aggregation of the amyloidogenic polypeptide IAPP (Islet Amyloid Polypeptide, amylin) is believed to play a direct role in the death of pancreatic β-islet cells in type II diabetes. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the progression of this disease. Here, we investigate myricetin's potential as an inhibitor of IAPP aggregation. We show that myricetin prevented thioflavin T binding in a concentration dependent manner. Atomic force microscopy revealed that myricetin prevented fiber formation under rigorous conditions conducive to forming IAPP aggregates. Using an IAPP-EGFP (Enhanced Green Fluorescent Protein) protein construct, we find that high concentrations of myricetin slowed the in vivo aggregation of IAPP-EGFP. Myricetin was also found to rescue living mammalian cells from the toxic effects of IAPP. These results indicate that myricetin is a strong inhibitor of IAPP amyloid aggregation and a potential lead molecule for the development of an amyloid inhibiting therapeutic.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/18/TOBIOCJ-6-66.PMC3394101.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30759471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 44

Model of Abnormal Chromophore-Protein Interaction for Е181К Rhodopsin Mutation: Computer Molecular Dynamics Study. Е181К紫红质突变的异常发色团-蛋白相互作用模型:计算机分子动力学研究。

Open Biochemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-08-16 DOI: 10.2174/1874091X01206010094

Tatyana Feldman, Mikhail Ostrovsky, Kholmirzo Kholmurodov, Kenji Yasuoka

{"title":"Model of Abnormal Chromophore-Protein Interaction for Е181К Rhodopsin Mutation: Computer Molecular Dynamics Study.","authors":"Tatyana Feldman, Mikhail Ostrovsky, Kholmirzo Kholmurodov, Kenji Yasuoka","doi":"10.2174/1874091X01206010094","DOIUrl":"10.2174/1874091X01206010094","url":null,"abstract":"The interaction of the 11-cis-retinal chromophore with the surrounding amino acid residues in the chromophore center of the rhodopsin protein has been investigated for the Е181К mutant form using molecular dynamics simulation. A comparative analysis of the arrangement of the amino acid residues in the chromophore center has been performed for both wild (native) and mutant rhodopsins. It is shown that for the Е181К mutant rhodopsin there is no proper binding of 11-cis-retinal with the surrounding amino acid residues. The distortion of the conformation states in the mutant rhodopsin molecule takes place in both the chromophore center and cytoplasmic domain. Our simulations suggest that a stable covalent linkage of 11-cis-retinal with the protein part (viz. opsin) of the rhodopsin molecule will not form. This, on the other hand, implies that the protein’s active site in the cytoplasmic domain, which is responsible for the G-protein binding (so-called transducin), may not be completely blocked. Based on our molecular simulation data, we discuss the possible correlation between retinitis pigmentosa pathogenesis and the structural and functional properties of the rhodopsin protein.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874091X01206010094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30867092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Protein Kinase A Subunit α Catalytic and A Kinase Anchoring Protein 79 in Human Placental Mitochondria. 人胎盘线粒体蛋白激酶A亚基α催化和A激酶锚定蛋白79。

Open Biochemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-04-11 DOI: 10.2174/1874091X01206010023

Maggie Pui Chi Ma, Murray Thomson

{"title":"Protein Kinase A Subunit α Catalytic and A Kinase Anchoring Protein 79 in Human Placental Mitochondria.","authors":"Maggie Pui Chi Ma, Murray Thomson","doi":"10.2174/1874091X01206010023","DOIUrl":"https://doi.org/10.2174/1874091X01206010023","url":null,"abstract":"Components of protein phosphorylation signalling systems have been discovered in mitochondria and it has been proposed that these molecules modulate processes including oxidative phosphorylation, apoptosis and steroidogenesis. We used electrophoresis and Western blots probed with specific antibodies to protein kinase A α catalytic subunit (PKAα Cat) and A kinase anchoring protein of approximately 79 kDa molecular weight (AKAP79) to demonstrate the presence of these two proteins in human placental mitochondria. Heavy mitochondria characteristic of cytotrophoblast were separated from light mitochondria characteristic of syncytiotrophoblast by centrifugation. PKAα Cat and AKAP79 were present in both heavy and light mitochondria with no significant difference in concentration. Sucrose density gradient separation of submitochondrial fractions indicated PKAα Cat is located predominantly in the outer membrane whereas AKAP79 is present mainly in the contact site fractions. These data indicate that PKAα Cat is present in the cytoplasm, nucleus and mitochondria of placental cells. AKAP79 is also present in human placental mitochondria but there may be anchoring proteins other than AKAP79 responsible for fixing PKA to the outer membrane. PKA may play roles in mitochondrial protein phosphorylation systems in both cytotrophoblast and syncytiotrophoblast.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/82/TOBIOCJ-6-23.PMC3330370.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40179300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Endoplasmic Reticulum (ER) Stress Enhances Tip60 (A Histone Acetyltransferase) Binding to the Concanavalin A. 内质网(ER)应激增强Tip60 (A组蛋白乙酰转移酶)与刀豆蛋白A的结合。

Open Biochemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-03-09 DOI: 10.2174/1874091X01206010001

Eun Jeoung Lee, Sung Hwa Shin, Sunghee Hyun, Jaesun Chun, Sang Sun Kang

{"title":"Endoplasmic Reticulum (ER) Stress Enhances Tip60 (A Histone Acetyltransferase) Binding to the Concanavalin A.","authors":"Eun Jeoung Lee, Sung Hwa Shin, Sunghee Hyun, Jaesun Chun, Sang Sun Kang","doi":"10.2174/1874091X01206010001","DOIUrl":"https://doi.org/10.2174/1874091X01206010001","url":null,"abstract":"Herein, we report that the concanavalin A binding of Tip60 (a target of the human immunodeficiency virus type 1-encoded transactivator Tat interacting protein 60 KD; a histone acetyltransferase; HAT) is enhanced as the result of endoplasmic reticulum (ER) stress. The cell expression of Tip60 combined with site-directed mutagenesis analysis was used to identify the glutamine 324 residue as the lecithin binding (Concanavalin A; Con A) site. The Tip60 N324A mutant strain, which seems to be the Con A binding-deficient, was attenuated the protein-protein interactions with FE65 and its protein stability, but its ability of G0-G1 cell cycle arrest was not interrupted. Interestingly, both HAT activity and the nuclear localization of Tip60 N324A mutant were enhanced than those of Tip60 WT. Thus, our results indicate that the Con A binding deficient of Tip60 seems to be one of the most pivotal posttranslational modifications (such as N-glycosylation) for its functional regulation signal, which is generated in response to ER stress.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874091X01206010001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30527607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Tianma modulates blood vessel tonicity. 天麻调节血管张力。

Open Biochemistry Journal Pub Date : 2012-01-01 Epub Date: 2012-06-14 DOI: 10.2174/1874091X01206010056

Lin Feng, Arulmani Manavalan, Manisha Mishra, Siu Kwan Sze, Jiang-Miao Hu, Klaus Heese

{"title":"Tianma modulates blood vessel tonicity.","authors":"Lin Feng, Arulmani Manavalan, Manisha Mishra, Siu Kwan Sze, Jiang-Miao Hu, Klaus Heese","doi":"10.2174/1874091X01206010056","DOIUrl":"https://doi.org/10.2174/1874091X01206010056","url":null,"abstract":"Tianma is a traditional Chinese medicine (TCM) often used for the treatment of hypertension and heart diseases. To elucidate the function of tianma at the molecular level, we investigated the effect of tianma on vascular functions and aortic protein metabolism. We found that long-term treatment with tianma (~2.5g/kg/day for three months) in one-year-old rats could enhance acetylcholine (ACh)-induced vasorelaxation in endothelium-intact thoracic aortic rings against both KCl (80 mM)- and phenylephrine (PE)-induced contraction. By using the iTRAQ (isobaric tag for relative and absolute quantification) technique, we confirmed from the functional data at the proteome level that tianma treatment down-regulated the expressions of contractile proteins (e.g. Acta2) and other related structural proteins (e.g. desmin), and up-regulated the expressions of extracellular matrix (ECM) glycoproteins (e.g. Fbln5) and anti-thrombotic proteins (e.g. Anxa2) in aortic tissue. By inductive reasoning, tianma could perform its vasodilatory effect not only by inhibiting vascular smooth muscle contraction, but also by enhancing blood vessel elasticity and stabilizing the arterial structure. Thus, tianma might become a novel therapeutic herbal medicine for cardiovascular diseases by regulating the aortic proteome metabolism.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874091X01206010056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30755931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

In the Huh7 Hepatoma Cells Diclofenac and Indomethacin Activate Differently the Unfolded Protein Response and Induce ER Stress Apoptosis. 在Huh7肝癌细胞中，双氯芬酸和吲哚美辛不同程度地激活未折叠蛋白反应并诱导内质网应激凋亡。

Open Biochemistry Journal Pub Date : 2011-01-01 Epub Date: 2011-09-23 DOI: 10.2174/1874091X01105010045

Silvia Franceschelli, Ornella Moltedo, Giuseppina Amodio, Gianfranco Tajana, Paolo Remondelli

{"title":"In the Huh7 Hepatoma Cells Diclofenac and Indomethacin Activate Differently the Unfolded Protein Response and Induce ER Stress Apoptosis.","authors":"Silvia Franceschelli, Ornella Moltedo, Giuseppina Amodio, Gianfranco Tajana, Paolo Remondelli","doi":"10.2174/1874091X01105010045","DOIUrl":"https://doi.org/10.2174/1874091X01105010045","url":null,"abstract":"Non-steroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenases (COXs) inhibitors frequently used in the treatment of acute and chronic inflammation. Side effects of NSAIDs are often due to their ability to induce apoptosis. Located at the Endoplasmic Reticulum membranes a tripartite signalling pathway, collectively known as the Unfolded Protein Response (UPR), decides survival or death of cells exposed to cytotoxic agents. To shed light on the molecular events responsible for the cytotoxicity of NSAIDs, we analysed the ability of diclofenac and indomethacin to activate the UPR in the human hepatoma cell line Huh7. We report that both NSAIDs can induce differently the single arms of the UPR. We show that indomethacin turns on the PERK and, only in part, the ATF6 and IRE1 pathways. Instead, diclofenac reduces the expression of ATF6 and does not stimulate the IRE1 endonuclease, which drives the expression of the prosurvival factor XBP1. Diclofenac, as well as indomethacin, is able to activate efficiently only the PERK pathway of the UPR, which induces the expression of the proapoptotic GADD153/CHOP protein. Our results highlight the importance of the UPR in evaluating the potential of drugs to induce apoptosis.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b4/ac/TOBIOCJ-5-45.PMC3182409.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30038089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

Production of free radicals and oxygen consumption by primary equine endothelial cells during anoxia-reoxygenation. 马内皮细胞在缺氧再氧化过程中自由基的产生和氧的消耗。

Open Biochemistry Journal Pub Date : 2011-01-01 Epub Date: 2011-11-24 DOI: 10.2174/1874091X01105010052

Geoffroy de Rebière de Pouyade, Alexandra Salciccia, Justine Ceusters, Ginette Deby-Dupont, Didier Serteyn, Ange Mouithys-Mickalad

{"title":"Production of free radicals and oxygen consumption by primary equine endothelial cells during anoxia-reoxygenation.","authors":"Geoffroy de Rebière de Pouyade, Alexandra Salciccia, Justine Ceusters, Ginette Deby-Dupont, Didier Serteyn, Ange Mouithys-Mickalad","doi":"10.2174/1874091X01105010052","DOIUrl":"https://doi.org/10.2174/1874091X01105010052","url":null,"abstract":"The endothelium plays an active role in ischemia/reperfusion injuries. Herein, we report the effect of a single or successive cycles of anoxia/reoxygenation (A/R) on the mitochondrial respiratory function of equine endothelial cells (cultured from carotids) monitored by high resolution oxymetry, and on their production of reactive oxygen species (ROS). ROS were measured by electron paramagnetic resonance (ESR) using POBN and DMPO spin traps, and by gas chromatography (GC) of ethylene released by ROS-induced α-keto-γ-(methylthio)butyric acid (KMB) oxidation. The oxygen consumption significantly decreased with the number of A/R cycles, and POBN-ESR spectra were specific of adducts formed in the cells from superoxide anion. After a one-hour A/R cycle, high intensity DMPO-ESR spectra were observed and assigned to superoxide anion trapping; the GC results confirmed an important production of ROS compared to normoxic cells. These results show that A/R induces mitochondrial alterations in endothelial cells, and strongly stimulates their oxidative activity as demonstrated by ESR and GC methods.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/de/TOBIOCJ-5-52.PMC3242399.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30355621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

New Perspectives of "omics" Applications in Melanoma Research. “组学”在黑色素瘤研究中的应用新视角。

Open Biochemistry Journal Pub Date : 2011-01-01 Epub Date: 2011-12-30 DOI: 10.2174/1874091X01105010060

Carmen Rodríguez-Cerdeira, Alberto Molares-Vila

{"title":"New Perspectives of \"omics\" Applications in Melanoma Research.","authors":"Carmen Rodríguez-Cerdeira, Alberto Molares-Vila","doi":"10.2174/1874091X01105010060","DOIUrl":"https://doi.org/10.2174/1874091X01105010060","url":null,"abstract":"Background: Oncoproteomics is the study of proteins and their interactions in a cancer cell by proteomic technologies and has the potential to revolutionize clinical practice, including cancer diagnosis. Recent technological advances in the analysis of the human genome have opened the door to improving our primitive understanding of the gene expression patterns in cancer. The examination of the phenotypic and (epi) genetic changes in cutaneous melanoma has identified several genes deemed central to the development and progression of melanoma.Methods: A review of the literature was performed to determine the role of epigenetic modifications in human melanoma. The role of array-based high-throughput gene expression analysis in understanding the specific genes involved as well as the pathways and the comparative gene expression patterns of primary and metastatic melanoma. The development and clinical application of selective pharmacologic agents are also discussed.Results: We identified several articles that have extensively studied the role of epigenetics in melanoma, further elucidating the complex processes involved in gene regulation and expression. Other studies utilizing gene microarray analysis and other whole genome approaches reveal a wide array of genes and expression patterns in human melanoma. Several genes have been identified as potential prognostic markers of tumor progression and overall clinical outcome.Conclusions: High-throughput gene expression analysis has had a major impact in melanoma research. Several gene expression platforms have provided insight into the gene expression patterns in melanoma. Such data will provide foundations for the future development of prognostic markers and improved targeted therapies for patients with melanoma.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874091X01105010060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30393110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

The Oxidative State of LDL is the Major Determinant of Anti/Prooxidant Effect of Coffee on Cu Catalysed Peroxidation. 低密度脂蛋白的氧化状态是咖啡对铜催化过氧化作用的抗/促氧化作用的主要决定因素。

Open Biochemistry Journal Pub Date : 2011-01-01 Epub Date: 2011-04-16 DOI: 10.2174/1874091X01105010001

Ciriaco Carru, Valeria Pasciu, Salvatore Sotgia, Angelo Zinellu, Maria Cristina Nicoli, Luca Deiana, Bruna Tadolini, Bastiano Sanna, Bruno Masala, Gianfranco Pintus

{"title":"The Oxidative State of LDL is the Major Determinant of Anti/Prooxidant Effect of Coffee on Cu Catalysed Peroxidation.","authors":"Ciriaco Carru, Valeria Pasciu, Salvatore Sotgia, Angelo Zinellu, Maria Cristina Nicoli, Luca Deiana, Bruna Tadolini, Bastiano Sanna, Bruno Masala, Gianfranco Pintus","doi":"10.2174/1874091X01105010001","DOIUrl":"https://doi.org/10.2174/1874091X01105010001","url":null,"abstract":"Antioxidants exert contrasting effect on low density lipoprotein (LDL) oxidation catalysed by metals, acting as pro-oxidants under select in vitro conditions. Through our study on the effect of coffee on LDL oxidation, we identified the parameters governing this phenomenon, contributing to the comprehension of its mechanism and discovering significant implications for correct alimentary recommendations. By measuring conjugated diene formation, we have analysed the quantitative and qualitative effects exerted by an extract of roasted coffee on LDL oxidation triggered by copper sulphate. When the relative effects of different coffee concentrations were plotted against the lag time (LT) of control LDL (C-LDL), the apparently random experimental data arranged in sensible patterns: by increasing the LT the antioxidant activity of coffee decreased progressively to become prooxidant. The critical LT, at which coffee switches from antioxidant to prooxidant, increased by increasing coffee concentration. Also the contrasting results obtained following a delayed addition of coffee to the assay, arranged in a simple pattern when referred to the LT of C-LDL: the prooxidant effect decreased to become antioxidant as the LT of C-LDL increased. The dependence of coffee effect on the LT of C-LDL was influenced by LDL but not by metal catalyst concentration. These novel findings point to the oxidative state of LDL as a major parameter controlling the anti/prooxidant effect of coffee and suggest the LT of C-LDL as a potent analytical tool to express experimental data when studying the action exerted by a compound on LDL oxidation.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d1/34/TOBIOCJ-5-1.PMC3104561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29907698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10

Parkin, A Top Level Manager in the Cell's Sanitation Department. 帕金是牢房卫生部门的高级经理。

Open Biochemistry Journal Pub Date : 2011-01-01 Epub Date: 2011-04-18 DOI: 10.2174/1874091X01105010009

Carolyn A Rankin, Ambrish Roy, Yang Zhang, Mark Richter

{"title":"Parkin, A Top Level Manager in the Cell's Sanitation Department.","authors":"Carolyn A Rankin, Ambrish Roy, Yang Zhang, Mark Richter","doi":"10.2174/1874091X01105010009","DOIUrl":"https://doi.org/10.2174/1874091X01105010009","url":null,"abstract":"Parkin belongs to a class of multiple RING domain proteins designated as RBR (RING, in between RING, RING) proteins. In this review we examine what is known regarding the structure/function relationship of the Parkin protein. Parkin contains three RING domains plus a ubiquitin-like domain and an in-between-RING (IBR) domain. RING domains are rich in cysteine amino acids that act as ligands to bind zinc ions. RING domains may interact with DNA or with other proteins and perform a wide range of functions. Some function as E3 ubiquitin ligases, participating in attachment of ubiquitin chains to signal proteasome degradation; however, ubiquitin may be attached for purposes other than proteasome degradation. It was determined that the C-terminal most RING, RING2, is essential for Parkin to function as an E3 ubiquitin ligase and a number of substrates have been identified. However, Parkin also participates in a number of other fiunctions, such as DNA repair, microtubule stabilization, and formation of aggresomes. Some functions, such as participation in a multi-protein complex implicated in NMDA activity at the post synaptic density, do not require ubiquitination of substrate molecules. Recent observations of RING proteins suggest their function may be regulated by zinc ion binding. We have modeled the three RING domains of Parkin and have identified a new set of RING2 ligands. This set allows for binding of two rather than just one zinc ion, opening the possibility that the number of zinc ions bound acts as a molecular switch to modulate Parkin function.","PeriodicalId":38958,"journal":{"name":"Open Biochemistry Journal","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/89/TOBIOCJ-5-9.PMC3104551.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29907700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 26