MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
批准号:
3226148
负责人:
IAN M ARMITAGE
金额:
$18.38万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1979
资助国家:
美国
项目状态:
已结题
起止时间:
1979-05-01 至 1991-04-30
关键词:
Escherichia coli affinity chromatography alkaline phosphatase aminoacid metabolism aminoacid transport binding proteins carbonate dehydratase carbonic anhydrase inhibitors catechol methyltransferase cations chemical binding chemical structure function enzyme structure enzyme substrate complex intestines kidney laboratory rabbit laboratory rat ligands ligase lipopolysaccharides membrane model membrane permeability membrane structure metalloenzyme metals methionine nuclear magnetic resonance spectroscopy pharmacology
中文摘要
总体目标是开发和应用最先进的核磁共振
测定溶液结构性质的技术
复杂的生物大分子,以阐明其机制
行动。 这些将研究的特定生物系统
方法是金属硫蛋白和环孢菌素结合蛋白,称为
亲环蛋白。
金属硫蛋白(MT):将使用多种NMR方法来充分
解决了这种结构和金属离子结合特性
普遍存在、金属离子诱导、低分子量、富含半胱氨酸
从各种物种中分离出来的金属结合蛋白,其长期
进化史(真菌、酵母、无脊椎动物和哺乳动物)。 这些
正是这种特性保证了这种蛋白质在生物体内的最终重要性。
必需金属(锌、铜)和非必需金属(镉、汞)的细胞调节
离子。 因此,这些研究将尽一切努力来阐明
这些不同MT结构的那些方面改变了它的
金属离子结合特性并将该数据与假设相关联,
但该蛋白质家族的功能尚未明确。
亲环蛋白是一种普遍存在的低分子量 (17 Kd) 胞质蛋白
对结合环孢菌素 A(一种有效的免疫抑制剂)具有高度特异性
临床用于预防肾、肝、心脏同种异体移植
拒绝。 具体目标是使用一维和二维
1H NMR 方法阐明溶液结构特性
亲环蛋白,特别是因为它们与结合位点有关
环孢菌素。 诸如此类的研究对于
了解该蛋白质在药理活性中的作用
环孢菌素及其活性代谢物及其结构活性
环孢菌素的关系。 长期目标是使用
NMR 与其他生化方法结合,可表征
当后者是亲环蛋白与其内在天然配体的复合物时
孤立的。 这些研究将为我们提供重要的新见解
环孢菌素的分子作用机制及其潜力
亲环蛋白在细胞调节中的生理意义
新陈代谢。
英文摘要
The overall objectives are to develop and apply state-of-the-art NMR
techniques to the determination of the solution structural properties of
complex biological macromolecules in order to elucidate their mechanism of
action. The specific biological systems that will be studied by these
methods are metallothioneins and a cyclosporin binding protein, termed
cyclophilin.
Metallothioneins (MTs): A variety of NMR methods will be used to fully
resolve both the structural and metal-ion binding properties of this
ubiquitous, metal-ion inducible, low molecular weight, cysteine-rich
metal-binding protein isolated from various species in its long
evolutionary history (fungus, yeast, invertebrate and mammalian). These
very properties assures the ultimate importance of this protein in the
cellular regulation of essential (Zn, Cu) and nonessential (Cd, Hg) metal
ions. As a result, every effort will be made in these studies to elucidate
those aspects of the structure of these different MTs which alter its
metal-ion binding properties and to correlate this data with the presumed,
but as yet undefined, function of this family of proteins.
Cyclophilin is a ubiquitous, low molecular weight (17 Kd) cytosolic protein
with high specificity for binding cyclosporin A, a potent immunosuppressant
used clinically for the prevention of kidney, liver and heart allograft
rejection. The specific objectives will be to use one and two-dimensional
1H NMR methods to elucidate the solution structural properties of
cyclophilin, particularly as they relate to the binding site for
cyclosporin. Studies such as these are of utmost importance to
understanding the role of this protein in the pharmacologic activity of
cyclosporin and its active metabolites, and the structure-activity
relationships for cyclosporin. The long-term objectives would be to use
NMR, in conjunction with other biochemical methods, to characterize the
complex of cyclophilin with its intrinsic natural ligand when the latter is
isolated. These studies would provide important new insight into the
molecular mechanism of action of cyclosporin and the potential
physiological significance of cyclophilin in the regulation of cellular
metabolism.
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TOWARD A PHYSICAL DESCRIPTION OF IMMUNOSUPPRESSION
-
批准号:3309007
-
项目类别:
-
资助金额:$22.87万
-
财政年份:1993
-
负责人:IAN M ARMITAGE
-
依托单位:
TOWARD A PHYSICAL DESCRIPTION OF IMMUNOSUPPRESSION
-
批准号:2187413
-
项目类别:
-
资助金额:$23.3万
-
财政年份:1993
-
负责人:IAN M ARMITAGE
-
依托单位:
TOWARD A PHYSICAL DESCRIPTION OF IMMUNOSUPPRESSION
-
批准号:2187411
-
项目类别:
-
资助金额:$23.75万
-
财政年份:1993
-
负责人:IAN M ARMITAGE
-
依托单位:
TOWARD A PHYSICAL DESCRIPTION OF IMMUNOSUPPRESSION
-
批准号:2187412
-
项目类别:
-
资助金额:$24.38万
-
财政年份:1993
-
负责人:IAN M ARMITAGE
-
依托单位:
HIGH FIELD NMR SPECTROMETER FOR BIOLOGICAL STUDIES
-
批准号:3519797
-
项目类别:
-
资助金额:$30.0万
-
财政年份:1987
-
负责人:IAN M ARMITAGE
-
依托单位:
PHYSICAL PROPERTIES OF LIPOPOLYSACCHARIDES
-
批准号:3130872
-
项目类别:
-
资助金额:$5.4万
-
财政年份:1984
-
负责人:IAN M ARMITAGE
-
依托单位:
PHYSICAL PROPERTIES OF LIPOPOLYSACCHARIDES
-
批准号:3130871
-
项目类别:
-
资助金额:$7.97万
-
财政年份:1984
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2137225
-
项目类别:
-
资助金额:$3.19万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2905207
-
项目类别:
-
资助金额:$19.34万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226144
-
项目类别:
-
资助金额:$19.19万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2518245
-
项目类别:
-
资助金额:$19.76万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226150
-
项目类别:
-
资助金额:$18.53万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2137224
-
项目类别:
-
资助金额:$16.08万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226149
-
项目类别:
-
资助金额:$19.41万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226146
-
项目类别:
-
资助金额:$19.7万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226142
-
项目类别:
-
资助金额:$22.55万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3151161
-
项目类别:
-
资助金额:$15.85万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:3226147
-
项目类别:
-
资助金额:$19.02万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2137227
-
项目类别:
-
资助金额:$19.03万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
MULTINUCLEAR NMR PROBES OF BIOLOGICAL SYSTEMS
-
批准号:2770345
-
项目类别:
-
资助金额:$18.87万
-
财政年份:1979
-
负责人:IAN M ARMITAGE
-
依托单位:
海外基金