Biochemical Society Symposia最新文献_第9页

Regulation of vascular function by haemoglobin. 血红蛋白调节血管功能

Biochemical Society Symposia Pub Date : 2004-01-01 DOI: 10.1042/bss0710135

Jack H Crawford, Balu K Chacko, Rakesh P Patel

引用次数: 3

Generation of bile pigments by haem oxygenase: a refined cellular strategy in response to stressful insults. 由血红素加氧酶生成胆汁色素:一种精致的细胞策略，以应对应激性侮辱。

Biochemical Society Symposia Pub Date : 2004-01-01 DOI: 10.1042/bss0710177

Roberta Foresti, Colin J Green, Roberto Motterlini

{"title":"Generation of bile pigments by haem oxygenase: a refined cellular strategy in response to stressful insults.","authors":"Roberta Foresti, Colin J Green, Roberto Motterlini","doi":"10.1042/bss0710177","DOIUrl":"https://doi.org/10.1042/bss0710177","url":null,"abstract":"The family of haem oxygenase enzymes is unique in nature for its role in haem degradation. Haem is cleaved at the alpha-meso position by haem oxygenase with the support of electrons donated by cytochrome P450 reductase, the first products of this reaction being CO, iron and biliverdin. Biliverdin is then converted to bilirubin by biliverdin reductase. If haem is viewed as a substrate for an anabolic pathway, it becomes evident that haem oxygenases do not break down haem for elimination from the body, but rather use haem to generate crucial molecules that can modulate cellular functions. The facts that biliverdin and bilirubin are potent antioxidants and that CO is both a vasoactive and signalling molecule sustain this idea. The existence of a constitutive haem oxygenase (HO-2), mainly present in the vasculature and nervous system, and an inducible haem oxygenase (HO-1), which is highly expressed during stress conditions in all tissues, also suggests that cells have evolved a fine control of this enzymic pathway to ultimately regulate haem consumption and to ensure production of CO, biliverdin/bilirubin and iron during physiological and pathophysiological situations. This review will focus primarily on the biological actions of biliverdin and bilirubin derived from the haem oxygenase/biliverdin reductase systems and their potential roles in counteracting oxidative and nitrosative stress.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 71","pages":"177-92"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1042/bss0710177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25013731","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: 70

Cofactor processing in galactose oxidase. 半乳糖氧化酶的辅因子加工。

Biochemical Society Symposia Pub Date : 2003-06-01 DOI: 10.1042/BST0310506

S. Firbank, M. Rogers, R. H. Guerrero, D. Dooley, M. Halcrow, S. Phillips, P. Knowles, M. McPherson

{"title":"Cofactor processing in galactose oxidase.","authors":"S. Firbank, M. Rogers, R. H. Guerrero, D. Dooley, M. Halcrow, S. Phillips, P. Knowles, M. McPherson","doi":"10.1042/BST0310506","DOIUrl":"https://doi.org/10.1042/BST0310506","url":null,"abstract":"GO (galactose oxidase; E.C. 1.1.3.9) is a monomeric 68 kDa enzyme that contains a single copper ion and an amino acid-derived cofactor. The enzyme is produced by the filamentous fungus Fusarium graminearum as an extracellular enzyme. The enzyme has been extensively studied by structural, spectroscopic, kinetic and mutational approaches that have provided insight into the catalytic mechanism of this radical enzyme. One of the most intriguing features of the enzyme is the post-translational generation of an organic cofactor from active-site amino acid residues. Biogenesis of this cofactor involves the autocatalytic formation of a thioether bond between Cys-228 and Tyr-272, the latter being one of the copper ligands. Formation of this active-site feature is closely linked to the loss of an N-terminal 17 amino acid prosequence. When copper and oxygen are added to this pro-form of GO (pro GO), purified in copper-free conditions from the heterologous host Aspergillus nidulans, mature GO is formed by an autocatalytic process. Structural comparison of pro GO with mature GO reveals overall structural similarity, but with some regions showing significant local differences in main-chain position. Some side chains of the active-site residues differ significantly from their positions in the mature enzyme. These structural effects of the prosequence suggest that it may act as an intramolecular chaperone to provide an open active-site structure conducive to copper binding and chemistry associated with cofactor formation. The prosequence is not mandatory for processing, as a recombinant form of GO lacking this region and purified under copper-free conditions can also be processed in an autocatalytic copper- and oxygen-dependent manner.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":"71 1","pages":"15-25"},"PeriodicalIF":0.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1042/BST0310506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"58414775","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: 23

Roles for asparagine endopeptidase in class II MHC-restricted antigen processing. 天冬酰胺内肽酶在II类mhc限制性抗原加工中的作用。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700031

Colin Watts, Daniela Mazzeo, Michelle A West, Stephen P Matthews, Doreen Keane, Garth Hamilton, Linda V Persson, Jennifer M Lawson, Bénédicte Manoury, Catherine X Moss

{"title":"Roles for asparagine endopeptidase in class II MHC-restricted antigen processing.","authors":"Colin Watts, Daniela Mazzeo, Michelle A West, Stephen P Matthews, Doreen Keane, Garth Hamilton, Linda V Persson, Jennifer M Lawson, Bénédicte Manoury, Catherine X Moss","doi":"10.1042/bss0700031","DOIUrl":"https://doi.org/10.1042/bss0700031","url":null,"abstract":"The adaptive immune response depends on the creation of suitable peptides from foreign antigens for display on MHC molecules to T lymphocytes. Similarly, MHC-restricted display of peptides derived from self proteins results in the elimination of many potentially autoreactive T cells. Different proteolytic systems are used to generate the peptides that are displayed as T cell epitopes on class I compared with class II MHC molecules. In the case of class II MHC molecules, the proteases that reside within the endosome/lysosome system of antigen-presenting cells are responsible; surprisingly, however, there are relatively few data on which enzymes are involved. Recently we have asked whether proteolysis is required simply in a generic sense, or whether the action of particular enzymes is needed to generate specific class II MHC-associated T cell epitopes. Using the recently identified mammalian asparagine endopeptidase as an example, we review recent evidence that individual enzymes can make clear and non-redundant contributions to MHC-restricted peptide display.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 70","pages":"31-8"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24051827","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: 8

Use of anti-neoepitope antibodies for the analysis of degradative events in cartilage and the molecular basis for neoepitope specificity. 使用抗新表位抗体分析软骨降解事件和新表位特异性的分子基础。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700107

John S Mort, Carl R Flannery, Joe Makkerh, Joanne C Krupa, Eunice R Lee

{"title":"Use of anti-neoepitope antibodies for the analysis of degradative events in cartilage and the molecular basis for neoepitope specificity.","authors":"John S Mort, Carl R Flannery, Joe Makkerh, Joanne C Krupa, Eunice R Lee","doi":"10.1042/bss0700107","DOIUrl":"https://doi.org/10.1042/bss0700107","url":null,"abstract":"Degradation of the cartilage proteoglycan, aggrecan, is an essential aspect of normal growth and development, and of joint pathology. The roles of different proteolytic enzymes in this process can be determined from the sites of cleavage in the aggrecan core protein, which generates novel termini (neoepitopes). Antibodies specific for the different neoepitopes generated by such cleavage events provide powerful tools with which to analyse these processes. The same approach can be used to differentiate the processed, active forms of proteases from their inactive pro-forms. Since the proteolytic processing of these enzymes requires the removal of the inhibitory pro-region, it also results in the generation of N-terminal neoepitopes. Using the newborn rat long bone as a model system, it was shown that the active form of ADAMTS-4 [ADAM (a disintegrin and metalloproteinase) with thrombospondin motifs-4], but not ADAMTS-5, co-localizes with the aggrecan cleavage neoepitopes known to be produced by this metalloproteinase. Thus, in long bone growth, aggrecan turnover seems to be dependent on ADAMTS-4 activity. To demonstrate the molecular basis of the specificity of anti-neoepitope antibodies, the Fv region of a monoclonal antibody specific for a neoepitope generated by the ADAMTS-4-mediated cleavage of aggrecan has been modelled and the binding of the peptide epitope simulated. In the docked structure, the N-terminus of the peptide antigen is clearly buried in the binding-site cavity. The absence of an open cleft makes it impossible for the intact substrate to pass through the binding site, providing a rationale for the specificity of this class of antibodies.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 70","pages":"107-14"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24051833","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: 31

Caspase activation. 半胱天冬酶激活。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1007/springerreference_66395

K. Boatright, G. Salvesen

引用次数: 117

Proteolytic 'defences' and the accumulation of oxidized polypeptides in cataractogenesis and atherogenesis. 蛋白水解“防御”和氧化多肽在白内障发生和动脉粥样硬化中的积累。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700135

Roger T Dean, Rachael Dunlop, Peter Hume, Ken J Rodgers

{"title":"Proteolytic 'defences' and the accumulation of oxidized polypeptides in cataractogenesis and atherogenesis.","authors":"Roger T Dean, Rachael Dunlop, Peter Hume, Ken J Rodgers","doi":"10.1042/bss0700135","DOIUrl":"https://doi.org/10.1042/bss0700135","url":null,"abstract":"Over the last few years, it has been clearly established that normal plasma contains low levels of oxidized polypeptides, and that these accumulate in tissues during several age-related pathologies. In contrast, normal mammalian aging, contrary to conventional dogma, is not clearly associated with enhanced levels of oxidized proteins, except in extracellular connective tissues, whose proteins can, for example, be oxidized by the neutrophil oxidative burst. Since mildly oxidized proteins are susceptible to accelerated degradation in most experimental systems, the question arises as to how the accumulation of oxidized proteins can take place. Such accumulation requires an excess of production (or deposition) over removal, which might reflect alterations in capacity or rate of production or removal. This chapter discusses our presently limited knowledge of rates and control of proteolysis of oxidized proteins in two pathologies, cataractogenesis and atherogenesis. It commences with a brief summary of current understanding of the mechanisms of protein oxidation, and of the observed accumulation of oxidized proteins in several pathologies.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 70","pages":"135-46"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24052375","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: 13

Memapsin 2, a drug target for Alzheimer's disease. Memapsin 2，阿尔茨海默病的药物靶点。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700213

Gerald Koelsch, Robert T Turner, Lin Hong, Arun K Ghosh, Jordan Tang

引用次数: 2

Collagen-platelet interactions: recognition and signalling. 胶原-血小板相互作用:识别和信号传导。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700081

Richard W Farndale, Pia R Siljander, David J Onley, Pavithra Sundaresan, C Graham Knight, Michael J Barnes

{"title":"Collagen-platelet interactions: recognition and signalling.","authors":"Richard W Farndale, Pia R Siljander, David J Onley, Pavithra Sundaresan, C Graham Knight, Michael J Barnes","doi":"10.1042/bss0700081","DOIUrl":"https://doi.org/10.1042/bss0700081","url":null,"abstract":"The collagen-platelet interaction is central to haemostasis and may be a critical determinant of arterial thrombosis, where subendothelium is exposed after rupture of atherosclerotic plaque. Recent research has capitalized on the cloning of an important signalling receptor for collagen, glycoprotein VI, which is expressed only on platelets, and on the use of collagen-mimetic peptides as specific tools for both glycoprotein VI and integrin alpha 2 beta 1. We have identified sequences, GPO and GFOGER (where O denotes hydroxyproline), within collagen that are recognized by the collagen receptors glycoprotein VI and integrin alpha 2 beta 1 respectively, allowing their signalling properties and specific functional roles to be examined. Triple-helical peptides containing these sequences were used to show the signalling potential of integrin alpha 2 beta 1, and to confirm its important contribution to platelet adhesion. Glycoprotein VI appears to operate functionally on the platelet surface as a dimer, which recognizes GPO motifs that are separated by four triplets of collagen sequence. These advances will allow the relationship between the structure of collagen and its haemostatic activity to be established.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 70","pages":"81-94"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24051831","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: 51

Control of the expression of inflammatory response genes. 控制炎症反应基因的表达。

Biochemical Society Symposia Pub Date : 2003-01-01 DOI: 10.1042/bss0700095

Jeremy Saklatvala, Jonathan Dean, Andrew Clark

{"title":"Control of the expression of inflammatory response genes.","authors":"Jeremy Saklatvala, Jonathan Dean, Andrew Clark","doi":"10.1042/bss0700095","DOIUrl":"https://doi.org/10.1042/bss0700095","url":null,"abstract":"The expression of genes involved in the inflammatory response is controlled both transcriptionally and post-transcriptionally. Primary inflammatory stimuli, such as microbial products and the cytokines interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF alpha), act through receptors of either the Toll and IL-1 receptor (TIR) family or the TNF receptor family. These cause changes in gene expression by activating four major intracellular signalling pathways that are cascades of protein kinases: namely the three mitogen-activated protein kinase (MAPK) pathways, and the pathway leading to activation of the transcription factor nuclear factor kappa B (NF kappa B). The pathways directly activate and induce the expression of a limited set of transcription factors which promote the transcription of inflammatory response genes. Many of the mRNAs are unstable, and are stabilized by the p38 MAPK pathway. Instability is mediated by clusters of the AUUUA motif in the 3' untranslated regions of the mRNAs. Control of mRNA stability provides a means of increasing the amplitude of a response and allows rapid adjustment of mRNA levels. Not all mRNAs stabilized by p38 contain AUUUA clusters; for example, matrix metalloproteinase-1 and -3 mRNAs lack these clusters, but are stabilized. Inflammatory gene expression is inhibited by glucocorticoids. These suppress MAPK signalling by inducing a MAPK phosphatase. This may be a significant mechanism additional to that by which the glucocorticoid receptor interferes with transcription factors.","PeriodicalId":55383,"journal":{"name":"Biochemical Society Symposia","volume":" 70","pages":"95-106"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24051832","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: 136