CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
批准号:
7598083
负责人:
EDVIN V POZHARSKIY
金额:
$0.81万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
已结题
起止时间:
2007-03-01 至 2008-02-29
关键词:
BindingComplexComputer Retrieval of Information on Scientific Projects DatabaseDataData CollectionDependenceDihydrofolate ReductaseDiseaseEnzymesEscherichia coliFolateFundingGlassGrantHydration statusInstitutionMolecularNADPOxidoreductasePlayProtein DynamicsProtein RegionProteinsResearchResearch PersonnelResolutionResourcesRoleSolventsSourceTemperatureUnited States National Institutes of Healthinterestprotein functionresearch study
中文摘要
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
蛋白质动力学在蛋白质功能中起着重要作用。正常的功能需要一定程度的内部流动性,当蛋白质经历所谓的玻璃化转变时,它们就失去了结合底物的能力。玻璃化转变在许多蛋白质中普遍发生在~180K,再加上结构和计算数据,导致假设它是由水合壳控制的,即蛋白质的动力学受制于溶剂。我们对超高温异丙基苹果酸脱氢酶(IPMDH)在不同温度下的蛋白质动力学的初步研究表明,该蛋白质的玻璃化转变移动到~250K。该实验包括在不同温度下以原子分辨率仔细研究IPMDH中的蛋白质动力学,以揭示超高温酶玻璃化转变的分子机制。此外,我们有兴趣使用类似的原子分辨率多温度数据收集策略来研究与NADP和叶酸结合的大肠杆菌二氢叶酸还原酶(DHFR)流产的三元复合体中蛋白质无序的温度依赖性。以前从这些晶体中收集的100K数据延伸到0.95°以上,并表明蛋白质的几个区域是无序的,这种无序可能与先前提出的催化相关的蛋白质动力学有关。然而,要确定这种紊乱的功能相关性,需要在酶能够催化氢化物转移的温度下收集衍射数据。
英文摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
Protein dynamics is known to play an important role in protein function. Certain level of internal mobility is required for proper function, and when proteins undergo so-called glass-transition, they lose the ability to bind substrates. Glass transition occurs universally at ~180K in many proteins, which together with the structural and computational data led to hypotheses that it is controlled by hydration shell, i.e. that protein dynamics is ¿enslaved¿ by solvent. Our preliminary study of protein dynamics in hyperthermophilic isopropylmalate dehydrogenase (IPMDH) at different temperatures indicates that glass-transition for this protein is shifted to ~250K. The proposed experiment includes careful examination of protein dynamics in IPMDH at atomic resolution at different temperatures in order to unravel the molecular mechanism of glass-transition in hyperthermophilic enzymes. Furthermore, we are interested in using a similar multi-temperature data collection strategy at atomic resolution to investigate the temperature dependence of protein disorder in an abortive ternary complex of E. coli dihydrofolate reductase (DHFR) bound to NADP+ and folate. Previous data collected from these crystals at 100 K extends to beyond 0.95 ¿ and indicates that several regions of the protein are disordered and that this disorder may be related to previously proposed catalytically relevant protein dynamics. However, establishing the functional relevance of this disorder requires diffraction data collected at a temperature at which the enzyme can catalyze hydride transfer.
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STUDIES OF INHIBITION OF MITOGEN ACTIVATED PROTEIN KINASE 1 (ERK2)
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批准号:8362294
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项目类别:
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资助金额:$0.27万
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财政年份:2011
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负责人:EDVIN V POZHARSKIY
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依托单位:
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
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批准号:8362066
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项目类别:
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资助金额:$0.03万
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财政年份:2011
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负责人:EDVIN V POZHARSKIY
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依托单位:
CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I
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批准号:8362121
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项目类别:
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资助金额:$0.19万
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财政年份:2011
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负责人:EDVIN V POZHARSKIY
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依托单位:
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
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批准号:8169955
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项目类别:
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资助金额:$0.03万
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财政年份:2010
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负责人:EDVIN V POZHARSKIY
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依托单位:
CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I
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批准号:8170032
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项目类别:
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资助金额:$0.51万
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财政年份:2010
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负责人:EDVIN V POZHARSKIY
-
依托单位:
STUDIES OF INHIBITION OF MITOGEN ACTIVATED PROTEIN KINASE 1 (ERK2)
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批准号:8170295
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项目类别:
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资助金额:$0.03万
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财政年份:2010
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负责人:EDVIN V POZHARSKIY
-
依托单位:
CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I
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批准号:7954347
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项目类别:
-
资助金额:$0.21万
-
财政年份:2009
-
负责人:EDVIN V POZHARSKIY
-
依托单位:
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
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批准号:7954230
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项目类别:
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资助金额:$0.02万
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财政年份:2009
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负责人:EDVIN V POZHARSKIY
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依托单位:
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
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批准号:7721858
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项目类别:
-
资助金额:$0.17万
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财政年份:2008
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负责人:EDVIN V POZHARSKIY
-
依托单位:
CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I
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批准号:7721999
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项目类别:
-
资助金额:$0.21万
-
财政年份:2008
-
负责人:EDVIN V POZHARSKIY
-
依托单位:
CRYSTALLOGRAPHIC STUDY OF CARBAMOYLPHOSPHATE SYNTHETASE TYPE I
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批准号:7598254
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项目类别:
-
资助金额:$0.02万
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财政年份:2007
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负责人:EDVIN V POZHARSKIY
-
依托单位:
CRYSTALLOGRAPHIC STUDY OF GLASS-TRANSITION IN HYPERTHERMOPHILIC ISOPROPYLMALATE
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批准号:7370581
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项目类别:
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资助金额:$0.47万
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财政年份:2006
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负责人:EDVIN V POZHARSKIY
-
依托单位:
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