Nitrite Inhibition of Carbon Monoxide Dehydrogenase
亚硝酸盐对一氧化碳脱氢酶的抑制
基本信息
- 批准号:9815924
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:Standard Grant
- 财政年份:1999
- 资助国家:美国
- 起止时间:1999-04-15 至 2000-03-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Acetate fermentation to methane accounts for two-thirds of the methane produced biologically in the environment. The central enzyme in the pathway of acetate utilization by methane-producing microorganisms is carbon monoxide dehydrogenase (CODH), a complex metalloenzyme that plays a critical role in both the synthesis and fermentation of acetate in anaerobic environments. In the methanogenic archaeon Methanosarcina thermophila, CODH catalyzes the cleavage of acetyl coenzyme A to produce free coenzyme A, a methyl group, and an enzyme-bound carbonyl that is subsequently oxidized to carbon dioxide. Despite the importance of CODH in biological methane production and in the anaerobic metabolism of acetate, the relationships between the structure and function of this complex metalloenzyme are only beginning to be elucidated.One strategy for investigating the mechanism of substrate binding and oxidation by CODH is examining the interaction of the enzyme with substrate analogs and inhibitors. Preliminary results in this laboratory have demonstrated that nitrite (NO2-) inhibits the catalytic activity of CODH from M. thermophila. This research project will utilize kinetic analysis and electron paramagnetic resonance (EPR) spectroscopy to investigate the mechanism by which nitrite inhibits CODH. The project has three specific objectives:1. To analyze the kinetics of nitrite inhibition of CODH in terms of type of inhibition, extent of reversibility, effects of pH and enzyme oxidation state, and effects of substrates and substrate analogs;2. To utilize EPR spectroscopy to identify which of the five known metal centers of CODH are affected by nitrite; and3. To determine if nitrite can be reduced as a novel substrate for CODH, possibly producing a reduced nitrogen compound such as nitric oxide (NO).The results of these experiments will define nitrite as a new inhibitor of CODH and will provide insight into the nature of nitrogen oxide interactions with the metal centers of the enzyme. Analysis of the kinetics of inhibition and the EPR properties of the inhibited enzyme will enable the investigators to (i) propose a likely mechanism for nitrite inhibition of CODH and (ii) test the possibility that nitrite is reduced as a substrate for CODH from M. thermophila. Information derived from these studies will serve as a foundation for future research focusing on the elucidation of the structure and mechanism of CODH from M. thermophila and the characterization of novel interactions of nitrogen oxides with metalloenzymes.
乙酸发酵生成甲烷占环境中生物产生的甲烷的三分之二。产甲烷微生物利用乙酸途径中的中心酶是一氧化碳脱氢酶(CODH),其是一种复杂的金属酶,在厌氧环境中乙酸的合成和发酵中起关键作用。在产甲烷古菌嗜热甲烷八叠球菌中,CODH催化乙酰辅酶A的裂解以产生游离辅酶A、甲基和随后被氧化成二氧化碳的酶结合的羰基。尽管CODH在生物甲烷生产和乙酸盐厌氧代谢中的重要性,但这种复杂的金属酶的结构和功能之间的关系才刚刚开始阐明,研究CODH底物结合和氧化机制的一个策略是研究酶与底物类似物和抑制剂的相互作用。本实验室的初步结果表明,亚硝酸盐(NO2-)抑制了M.嗜热菌本研究计画将利用动力学分析及电子顺磁共振光谱来探讨亚硝酸盐抑制CODH的机制。该项目有三个具体目标:1。 从抑制类型、可逆程度、pH和酶氧化态的影响以及底物和底物类似物的影响等方面分析亚硝酸盐对CODH的抑制动力学;2. 利用电子顺磁共振光谱来鉴定CODH的五个已知金属中心中的哪一个受到亚硝酸盐的影响; 为了确定亚硝酸盐是否可以被还原为CODH的新底物,可能产生还原的氮化合物,如一氧化氮(NO),这些实验的结果将定义为一种新的CODH抑制剂亚硝酸盐,并将提供洞察的性质,氮氧化物与金属中心的酶的相互作用。对抑制动力学和被抑制酶的EPR性质的分析将使研究人员能够(i)提出亚硝酸盐抑制CODH的可能机制,(ii)测试亚硝酸盐作为来自M的CODH的底物被还原的可能性。嗜热菌这些研究结果为进一步阐明木霉CODH的结构和作用机制奠定了基础。嗜热菌和氮氧化物与金属酶的新型相互作用的表征。
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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Madeline Rasche其他文献
Madeline Rasche的其他文献
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{{ truncateString('Madeline Rasche', 18)}}的其他基金
RUI: Electron Transfer and Inhibition of Dihydromethanopterin Reductase
RUI:二氢甲烷蝶呤还原酶的电子转移和抑制
- 批准号:
1508801 - 财政年份:2015
- 资助金额:
-- - 项目类别:
Continuing Grant
Methanopterin Biosynthesis in Archaea and Methylotrophic Bacteria
古细菌和甲基营养细菌中的甲烷蝶呤生物合成
- 批准号:
1020200 - 财政年份:2009
- 资助金额:
-- - 项目类别:
Continuing Grant
CAREER: Methanopterin Biosynthesis in Archaea and Methylotrophic Bacteria
职业:古细菌和甲基营养细菌中的甲烷蝶呤生物合成
- 批准号:
9876212 - 财政年份:1999
- 资助金额:
-- - 项目类别:
Continuing grant
Minority Postdoctoral Research Fellowship
少数族裔博士后研究奖学金
- 批准号:
9308049 - 财政年份:1993
- 资助金额:
-- - 项目类别:
Fellowship Award
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