SULFATION OF HUMAN PLASMA PROTEIN
人血浆蛋白的硫酸化
基本信息
- 批准号:3294561
- 负责人:
- 金额:$ 13.31万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1993
- 资助国家:美国
- 起止时间:1993-01-01 至 1996-06-30
- 项目状态:已结题
- 来源:
- 关键词:active sites animal tissue antithrombin III blood chemistry blood proteins calorimetry chemical cleavage circular dichroism coagulation factor V coagulation factor VIII complement enzyme activity enzyme inhibitors enzyme substrate fibrinogen fibronectins high performance liquid chromatography human tissue immunoaffinity chromatography intermolecular interaction nuclear magnetic resonance spectroscopy plasmin protein purification stoichiometry sulfation sulfotransferase synthetic peptide thrombin tissue /cell culture tyrosine urinalysis vitronectin
项目摘要
Sulfation of tyrosine residues is a biosynthetic modification of
physiologically important plasma proteins including the fourth component
of complement, coagulation factors V and VIII, fibronectin, and alpha2-
antiplasmin. In several of these examples, it is recognized that their
sulfation has major effects on activity. We hypothesize that sites of
sulfation often serve as recognition elements and points of contact in
protein-protein interactions. The current proposal examines this
hypothesis and extends our previous work on the biosynthesis and
function of tyrosine sulfate residues in plasma proteins. Objectives
are: 1) To define the roles of tyrosine sulfate residues in interactions
of coagulation, fibrinolytic, and complement components, 2) To examine
the stoichiometry and physiological variation of tyrosine sulfation, and
3) To identify recognition signals that direct the sulfation of specific
sites.
Contributions of sulfate groups to interactions of plasma proteins with
the proteinases thrombin, plasmin, and the C1s subcomponent of
complement will be studied by comparing activities of sulfated and
nonsulfated forms of proteins and of synthetic peptides corresponding to
sites of sulfation. Activities will be assessed with functional
complement and coagulation assays and with purified enzymes. The
affinities and thermodynamics of the binding of peptides to proteins
will be measured by titration calorimetry. It is not known whether
there is physiological or pathological variation in the sulfation of
proteins. This issue will be studied by measuring the tyrosine sulfate
content of several plasma proteins and of urine from different
individuals. Specific proteins will be purified by immunoaffinity
methods and their tyrosine sulfate content assessed by amino acid
analysis of base hydrolysates or by HPLC analysis of peptides produced
by proteolytic or chemical cleavage. A series of synthetic peptides
will be studied as substrates of tyrosylprotein sulfotransferase to
determine how substrate sites are identified, to provide optimal
substrates for assay and affinity purification of the enzyme, and to
serve as a basis for designing inhibitors. Long term goals are to
understand the physiological significance and variation of the sulfation
of tyrosine residues in proteins. In addition, this work will provide
basic information about interactions between coagulation and complement
components.
酪氨酸残基的硫酸化是酪氨酸的生物合成修饰。
包括第四组分的生理学上重要的血浆蛋白
补体、凝血因子V和VIII、纤连蛋白和α 2-
抗纤溶酶 在其中的几个例子中,人们认识到,
硫酸化作用对活性有重要影响。 我们假设,
硫酸化作用通常用作识别元件和接触点,
蛋白质相互作用 目前的建议审查了这一点
假设并扩展了我们之前关于生物合成和
酪氨酸硫酸盐残基在血浆蛋白中的功能。 目标
主要有:1)确定酪氨酸硫酸酯残基在相互作用中的作用
凝血、纤溶和补体成分,2)检查
酪氨酸硫酸化的化学计量和生理变化,以及
3)为了识别识别信号,指导特定的硫酸化,
网站.
硫酸根基团对血浆蛋白与蛋白质相互作用的贡献
蛋白酶凝血酶、纤溶酶和C1 s亚组分
将通过比较硫酸化和
非硫酸化形式的蛋白质和合成肽,
硫酸化位点。 活动将通过功能评估
补体和凝血测定以及纯化的酶。 的
肽与蛋白质结合的亲和力和热力学
将通过滴定量热法测量。 目前还不知道是否
在硫酸化中存在生理或病理变化,
proteins. 本课题将通过测定酪氨酸硫酸盐来研究
几种血浆蛋白和尿液的含量,
个体 特异性蛋白质将通过免疫亲和纯化
方法及其用氨基酸法测定的酪氨酸硫酸盐含量
碱水解产物分析或通过HPLC分析产生的肽
通过蛋白水解或化学裂解。 一系列合成肽
将作为酪蛋白磺基转移酶的底物进行研究,
确定如何识别底物位点,以提供最佳的
用于酶的测定和亲和纯化的底物,以及
作为设计抑制剂的基础。 长期目标是
了解硫酸化的生理意义和变化
蛋白质中的酪氨酸残基。 此外,这项工作将提供
关于凝血和补体之间相互作用的基本信息
件.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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