THERMODYNAMIC MODEL FOR LIGAND-INDUCED BIPHASIC PROTEIN DENATURATION
THERMODYNAMIC MODEL FOR LIGAND-INDUCED BIPHASIC PROTEIN DENATURATION
批准号:
3811131
负责人:
ANDREW F SHRAKE
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
根据实验数据(Vox Sang. 47,7-18(1984)和J. Biol.
Chem 263,15392-15399(1988)],其衍生自热诱导
人白蛋白的变性研究,我们得出结论,
蛋白质的双相变性,与蛋白质无关
如果蛋白质对配体的亲和力
是足够大的,如果最初的蛋白质是不饱和的配体。
近似计算表明,这种描述可以解释
第42届量热会议摘要(1987)。
我们已经开发了一个严格的热力学模型,其中包括
配体结合对去折叠转变温度的影响
并且已经证明了对蛋白质的计算,
具有三个不同亲和常数值的单个结合位点
可以再现观察到的白蛋白变性的显著特征
在低、中和高亲和力配体的存在下[J. Biol.
Chem. 265,50555059(1990))。目前我们正在进行更详细的
使用文献中的结合数据计算白蛋白,
为了证明热力学模型的计算结果,
这些变性特征与实验观察到的那些非常相似。在
此外,我们计划用配体诱导的双相
变性,不同的蛋白质对变性谱的贡献
天然蛋白质种类通常不具有双态性质
这表明标准的反卷积程序将导致一个基础
一组缺乏物理意义的组成吸热曲线。而且有
对双峰起源的理论研究表明,
多相(即,三相等)变性可以发生,并揭示了
造成这一现象的因素。
英文摘要
On the basis of experimental data (Vox Sang. 47, 7-18 (1984) and J. Biol.
Chem 263, 15392-15399 (1988)], which derive from thermally induced
denaturation studies of human albumin, we concluded that ligand-induced
biphasic denaturation of the protein, which does not relate to protein
domain substructure can occur if the affinity of the protein for the ligand
is great enough and if initially the protein is subsaturated with ligand.
Approximate calculations indicated that such a description can account for
these observations (Abstracts of the 42nd Calorimetry Conference (1987)].
We have developed a rigorous thermodynamic model, which incorporates the
effects of ligand binding on the transition temperature for the unfolding
of the protein and have demonstrated that a computation for a protein with
a single binding site with three different values for the affinity constant
can reproduce the salient features of the observed denaturation of albumin
in the presence of low, intermediate, and high affinity ligands [J. Biol.
Chem. 265, 50555059 (1990)). Currently we are carrying out more detailed
calculations for albumin, utilizing binding data in the literature, in
order to demonstrate that the thermodynamic model results in computed
denaturation profiles that closely mimic those observed experimentally. In
addition, we plan to illustrate that with ligand-induced biphasic
denaturation, contributions to the denaturation profile by the different
native protein species are in general not of a two-state nature thereby
indicating that standard deconvolution procedures would result in a basis
set of constitutive endotherms devoid of physical meaning. Furthermore, a
theoretical investigation of the origins of bimodality demonstrates that
multiphasic (i.e., triphasic etc.) denaturation can occur and reveals the
factors responsible for this phenomenon.
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PHYSICAL CHARACTERIZATION OF SYNTHETIC PLASMA VOLUME EXPANDERS
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批准号:3811132
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:
Characterization of Non-Protein Colloidal Plasma Volume
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批准号:6680016
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
PROTEIN STABILITY AND FOLDING/UNFOLDING AND FORMATION OF PRIONS AND OTHER DELETER
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批准号:6293806
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
CHARACTERIZATION OF NON-PROTEIN COLLOIDAL PLASMA VOLUME EXPANDERS
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批准号:6293807
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
Characterization of Colloidal Plasma Volume Expanders
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批准号:6546127
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
MECHANISMS OF PROTEIN FOLDING
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批准号:3811133
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:
Stability, Folding and Formation of Deleterious Proteins
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批准号:6546124
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
Protein Stability, Folding/Unfolding, and Formation of D
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批准号:6680015
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
Characterization of Non-Protein Colloidal Plasma Volume Expanders
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批准号:6433596
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
Protein Stability and Folding/Unfolding and Formation of Prions and Other Delet
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批准号:6433595
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
Protein Stability, Folding/Unfolding, and Formation of D
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批准号:6839882
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项目类别:
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资助金额:$0.0万
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财政年份:--
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负责人:ANDREW F SHRAKE
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依托单位:--
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