STUDIES ON THE ACTIVE SITES AND MECHANISMS OF CYTOCHROME P450
细胞色素P450活性位点及机制研究
基本信息
- 批准号:3853571
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
The cytochromes P450 are a family of isozymes capable of oxidizing a wide
variety of both endogenous and exogenous compounds. Two characteristics
of these enzymes make it possible for a limited number of isozymes to
metabolize a vast and varied array of chemical compounds. The first is
the generally broad substrate and regiospecificity presumably due to
relatively nonspecific substrate binding characteristics and multiple
binding orientations. The second is a versatile active oxygenating
species that is capable of oxidizing a variety of functional groups. The
goal of this research is to explore the mechanisms of oxygen activation,
substrate oxidation and the topology of the P450 active sites. Methods
used in the project include recombinant DNA techniques, determination of
enzyme and isotope effect kinetics, and kinetic analysis of both wild
type and mutant enzymes. In the past, we have derived several equations
for comprehensive kinetic models to describe the observed kinetic isotope
effects on cytochrome P450 catalyzed oxidations. These models suggest
that the observed isotope effects can provide information on both binding
conformations and the amount of uncoupled electron flux that results in
water formation. Previous studies on the metabolism of testosterone by
several of the expressed P450 isozymes and their chimeric and mutant
forms (developed by Dr. Frank Gonzalez) revealed that modification of a
few amino acid residues in critical positions can markedly affect the
pattern of metabolites. We are now in the process of performing full
kinetic analyses, including isotope effect experiments, and stoichiometry
experiments to characterize wild-type enzymes and the effect of the
mutations on the enzyme mechanisms.
细胞色素P450是一个同工酶家族,能够氧化一个宽
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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K KORZEKWA其他文献
K KORZEKWA的其他文献
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{{ truncateString('K KORZEKWA', 18)}}的其他基金
STUDIES ON THE CONVERSION OF ANDROGENS TO ESTROGENS BY AROMATASE
芳香酶将雄激素转化为雌激素的研究
- 批准号:
3838486 - 财政年份:
- 资助金额:
-- - 项目类别:
THEORETICAL MODELS FOR CYTOCHROME P-450 MEDIATED HYDROGEN ATOM ABSTRACTION
细胞色素 P-450 介导的氢原子抽象的理论模型
- 批准号:
3878919 - 财政年份:
- 资助金额:
-- - 项目类别:
STUDIES ON THE ACTIVE SITES AND MECHANISMS OF CYTOCHROME P450
细胞色素P450活性位点及机制研究
- 批准号:
3752725 - 财政年份:
- 资助金额:
-- - 项目类别:
STUDIES ON THE ACTIVE SITES AND MECHANISMS OF CYTOCHROME P450
细胞色素P450活性位点及机制研究
- 批准号:
3838460 - 财政年份:
- 资助金额:
-- - 项目类别:
THEORETICAL MODELS FOR CYTOCHROME P450 MEDIATED OXIDATIONS
细胞色素 P450 介导的氧化的理论模型
- 批准号:
3838459 - 财政年份:
- 资助金额:
-- - 项目类别:
THEORETICAL MODELS FOR CYTOCHROME P450 MEDIATED OXIDATIONS
细胞色素 P450 介导的氧化的理论模型
- 批准号:
3853570 - 财政年份:
- 资助金额:
-- - 项目类别:
A UNIQUE TESTOSTERONE METABOLITE--17BETA-HYDROXY 4,6-ANDROSTADIENE-3-ONE
一种独特的睾酮代谢物--17β-羟基4,6-雄甾二烯-3-酮
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3920011 - 财政年份:
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