DYNAMICS OF GLUTATHIONE TRANSFERASE A1-1
谷胱甘肽转移酶 A1-1 的动力学
基本信息
- 批准号:7956237
- 负责人:
- 金额:$ 0.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-08-01 至 2010-07-31
- 项目状态:已结题
- 来源:
- 关键词:BindingBiomedical ResearchComplementComplexComputer Retrieval of Information on Scientific Projects DatabaseDockingDrug Metabolic DetoxicationEnzymesFundingFutureGlutathioneGlutathione S-TransferaseGrantHigh Performance ComputingHomoHousingHumanInstitutionLaboratoriesLigandsMolecular WeightMutationNMR SpectroscopyOutcomePropertyProtein DynamicsProtein IsoformsProteinsResearchResearch PersonnelResourcesRunningServicesSourceSystemUnited States National Institutes of Healthalpha helixdimerenzyme structureglutathione transferase A1-1molecular mechanicsmutantresearch study
项目摘要
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.
Glutathione transferases (GST) are detoxification enzymes that inactivate reactive hydrophobic compounds by conjugating the tripeptide glutathione to reactive centers on these compounds. We have been using NMR spectroscopy to characterize the dynamic properties of one human isoform, GST A1-1. We have shown that the carboxy-terminal alpha helix becomes docked when either substrate or product bind to the enzyme. Currently we are generating mutations in the protein that may be responsible for stabilizing the docked form of this helix and investigating the enzymatic and dynamic properties of these enzymes. To complement the NMR studies, we would like to investigate the effects of these mutations on the dynamics of the protein using molecular mechanics calculations. We feel that the molecular mechanics calculations will aid in the interpretation of our laboratory date and may provide a means to predict the outcome of future experiments. The protein is a homo-dimer of 50,000 kDa overall molecular weight. We would like to perform dynamics calculations on the wild-type enzyme and three mutants (Ile219Ala, Phe220Ala, Phe222Ala, for both the unliganded and the enzyme-product complex. The crystal structure of the enzyme-product complex will be used for starting coordinates. We intend to employ CHARMM using a solvated system with periodic boundary conditions. We will initially perform dynamics runs for ~5ns to gauge whether there are significant difference between the eight different forms of the protein (apo + liganded/wildtype + 3 mutants). We anticipate equilibration of the system in-house on our sgi origin 300 server. Please allocate the appropriate number of service units.
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。
谷胱甘肽转移酶(GST)是一种解毒酶,通过将三肽谷胱甘肽结合到活性疏水化合物上的活性中心来使这些化合物失活。我们一直在使用核磁共振波谱来表征一个人类亚型GST A1-1的动态性质。我们已经证明,当底物或产物与酶结合时,羧基末端的α螺旋变得对接。目前,我们正在蛋白质中产生突变,这可能负责稳定这种螺旋的对接形式,并研究这些酶的酶学和动力学性质。为了补充核磁共振研究,我们想用分子力学计算来研究这些突变对蛋白质动力学的影响。我们认为,分子力学计算将有助于解释我们的实验室数据,并可能提供一种方法来预测未来实验的结果。该蛋白质是一种总分子量为50,000 kDa的同源二聚体。我们想要对野生型酶和三个突变体(Ile219Ala,Phe220Ala,Phe222Ala,对于无连接和酶-产物复合体)进行动力学计算。酶-产物复合体的晶体结构将被用作起始坐标。我们打算使用具有周期边界条件的解化系统的CHARMM。我们最初将进行~5 ns的动力学运行,以衡量8种不同形式的蛋白质(apo+配基/野生型+3个突变体)之间是否存在显著差异。我们预计在我们的SGI Origin 300服务器上实现内部系统平衡。请分配适当数量的服务单位。
项目成果
期刊论文数量(0)
专著数量(0)
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{{ truncateString('GORDON RULE', 18)}}的其他基金
STRUCTURAL DEPENDENCE OF PHOSPHOLIPIDS ON DIVALENT CALCIUM ION
磷脂对二价钙离子的结构依赖性
- 批准号:
6319789 - 财政年份:1999
- 资助金额:
$ 0.08万 - 项目类别:
STRUCTURAL DEPENDENCE OF PHOSPHOLIPIDS ON DIVALENT CALCIUM ION
磷脂对二价钙离子的结构依赖性
- 批准号:
6295211 - 财政年份:1998
- 资助金额:
$ 0.08万 - 项目类别:
STRUCTURAL DEPENDENCE OF PHOSPHOLIPIDS ON DIVALENT CALCIUM ION
磷脂对二价钙离子的结构依赖性
- 批准号:
6122521 - 财政年份:1998
- 资助金额:
$ 0.08万 - 项目类别:
STRUCTURAL DEPENDENCE OF PHOSPHOLIPIDS ON DIVALENT CALCIUM ION
磷脂对二价钙离子的结构依赖性
- 批准号:
6282556 - 财政年份:1998
- 资助金额:
$ 0.08万 - 项目类别:
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