DESIGN OF REDOX ACTIVE METAL HEME HYDRID ENZYMES
氧化还原活性金属血红素氢化酶的设计
基本信息
- 批准号:6314098
- 负责人:
- 金额:$ 12.33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2000
- 资助国家:美国
- 起止时间:2000-06-01 至 2001-05-31
- 项目状态:已结题
- 来源:
- 关键词:active sites binding sites calorimetry cofactor cytochrome c peroxidase electrochemistry electron crystallography electron spin resonance spectroscopy electron transport enzyme mechanism green fluorescent proteins hemoprotein hybrid enzyme intermolecular interaction manganese mass spectrometry metalloenzyme molecular biology information system oxidation reduction reaction peptide chemical synthesis protein structure function thermodynamics
项目摘要
The overall goals of this proposal are to introduce, by design, a series of binding sites for redox active metal centers near the pre-exiting heme co-factor of an oxidative heme enzyme in order to study the electron-transfer, electronic coupling, and redox reactions that result from the interaction of the two metal centers. Such binuclear metalloprotein complexes may serve as mechanistic and functional models of naturally occurring enzymes such as manganese dependent ligninase and cytochrome c oxidase. Metal binding sites have been introduced into cytochrome c peroxidase near the heme periphery that result in significantly enhanced enzyme dependent oxidation of Mn+2 ions by H2O2. Continued studies will provide insights in two distinctly different arenas: 1) By comparing the kinetics, spectroscopy, energetics and co- factor dependence of these hybrids, significant insight may be obtain into the relative importance of parameters such as ligand environment, metal-heme coupling, and redox thermodynamics. Thus, these studies may provide answers to unresolved questions about the function of natural systems containing interacting heme and metal centers. 2) The accumulation of new information on the binding specificity, thermodynamics and structural parameters of several related designed metal binding sites in the context of a well characterized model protein framework containing a second redox active co-factor will provide important input for the overall design goals of the metalloprotein design program. The experiments in project VII are meant to complement work on other designed metalloproteins, yet focus upon details of metal- co-factor interactions. In addition, we will perform supporting and collaborative studies within the program project to help characterize designed metal sites near the chromophore of green fluorescent protein (GFP). EPR, electrochemistry, calorimetry and fluorescence kinetics experiments intended to explore the effects of metal binding on the properties of the chromophore will provide significant feedback on these project components. In this way, the proposed studies will directly impact on the central themes of the program project by contributing to a rule base for the design and evaluation of metal sites within protein structures for the purpose of controlling the regulation, folding and function of novel metalloproteins.
该提案的总体目标是通过设计引入一系列氧化还原活性金属中心的结合位点,这些结合位点靠近氧化血红素酶的预先存在的血红素辅因子,以研究电子转移、电子耦合和氧化还原反应,这些反应是由两个金属中心的相互作用引起的。这种双核金属蛋白复合物可以作为天然存在的酶,如锰依赖性木质素酶和细胞色素c氧化酶的机理和功能模型。金属结合位点已被引入到细胞色素c过氧化物酶附近的血红素周边,导致显着增强的酶依赖性氧化Mn+2离子的H2 O2。继续的研究将在两个明显不同的领域中提供见解:1)通过比较这些杂化物的动力学、光谱学、能量学和辅因子依赖性,可以获得对诸如配体环境、金属-血红素偶联和氧化还原热力学的参数的相对重要性的显著见解。因此,这些研究可能会提供答案,尚未解决的问题,自然系统的功能,含有相互作用的血红素和金属中心。2)积累的新信息的结合特异性,热力学和结构参数的几个相关的设计金属结合位点的背景下,一个良好的表征模型蛋白质框架包含第二氧化还原活性辅因子将提供重要的输入的金属蛋白设计程序的总体设计目标。项目VII中的实验旨在补充其他设计的金属蛋白的工作,但重点是金属-辅因子相互作用的细节。此外,我们将在该计划项目中进行支持和合作研究,以帮助表征绿色荧光蛋白(GFP)发色团附近的设计金属位点。EPR、电化学、量热和荧光动力学实验旨在探索金属结合对发色团性质的影响,这些实验将为这些项目组件提供重要的反馈。通过这种方式,拟议的研究将直接影响该计划项目的中心主题,为蛋白质结构内金属位点的设计和评估提供规则基础,以控制新型金属蛋白的调节,折叠和功能。
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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DAVID B. GOODIN其他文献
DAVID B. GOODIN的其他文献
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{{ truncateString('DAVID B. GOODIN', 18)}}的其他基金
CHARACTERIZATION OF MOLECULAR WIRES BOUND TO P450CAM, CCP, AND INOS
与 P450CAM、CCP 和 INOS 结合的分子线的表征
- 批准号:
8362151 - 财政年份:2011
- 资助金额:
$ 12.33万 - 项目类别:
CHARACTERIZATION OF MOLECULAR WIRES BOUND TO P450CAM, CCP, AND INOS
与 P450CAM、CCP 和 INOS 结合的分子线的表征
- 批准号:
8170093 - 财政年份:2010
- 资助金额:
$ 12.33万 - 项目类别:
CHARACTERIZATION OF MOLECULAR WIRES BOUND TO P450CAM, CCP, AND INOS
与 P450CAM、CCP 和 INOS 结合的分子线的表征
- 批准号:
7954420 - 财政年份:2009
- 资助金额:
$ 12.33万 - 项目类别:
CHARACTERIZATION OF MOLECULAR WIRES BOUND TO P450CAM, CCP, AND INOS
与 P450CAM、CCP 和 INOS 结合的分子线的表征
- 批准号:
7722111 - 财政年份:2008
- 资助金额:
$ 12.33万 - 项目类别:
HIGH RESOLUTION SAR STUDIES ON CAVITY MUTANTS OF CYTOCHROME C PEROXIDASE
细胞色素C过氧化物酶空腔突变体的高分辨率SAR研究
- 批准号:
7370386 - 财政年份:2006
- 资助金额:
$ 12.33万 - 项目类别:
HIGH RESOLUTION CRYSTALLOGRAPHY OF HEME ENZYMES WITH SUBSTRATE-LINKED SENSITIZER
具有底物连接敏化剂的血红素酶的高分辨率晶体学
- 批准号:
7370385 - 财政年份:2006
- 资助金额:
$ 12.33万 - 项目类别:
HIGH RES SAR OF CAVITY MUTANTS OF CYTOCHROME C PEROXIDAS
细胞色素 C 过氧化物空腔突变体的高分辨率 SAR
- 批准号:
6976274 - 财政年份:2004
- 资助金额:
$ 12.33万 - 项目类别:
Redox-Active and Luminescent Probes for Heme Enzymes
用于血红素酶的氧化还原活性和发光探针
- 批准号:
6940828 - 财政年份:2004
- 资助金额:
$ 12.33万 - 项目类别:
Redox-Active and Luminescent Probes for Heme Enzymes
用于血红素酶的氧化还原活性和发光探针
- 批准号:
6764840 - 财政年份:2004
- 资助金额:
$ 12.33万 - 项目类别:
Redox-Active and Luminescent Probes for Heme Enzymes
用于血红素酶的氧化还原活性和发光探针
- 批准号:
7119204 - 财政年份:2004
- 资助金额:
$ 12.33万 - 项目类别:
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