MECHANISMS FOR ENZYME CATALYSIS OF HETEROLYTIC REACTIONS
酶催化杂解反应的机制
基本信息
- 批准号:3306773
- 负责人:
- 金额:$ 14.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-05-01 至 1996-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Several problems are presented that are directly related to the mechanism
for enzymatic catalysis of aldose-ketose isomerization reactions,
glycosyl transfer reactions and aldol condensation reactions. The
solutions to these problems have eluded investigations employing some of
the most sophisticated experimental methods of mechanistic enzymology.
This proposal describes how these problems may be resolved by an
application of the tools and principles of physical organic chemistry.
Three different projects are described.
(1) It is not known whether the nonenzymatic or enzyme-catalyzed
isomerization reactions of sugars proceed by a hydride or a proton
transfer mechanism, or if general acids and metal ions are effective
catalysts of these reactions. Questions about the nonenzymatic reactions
will be resolved by a study of the isomerization of glyceraldehyde and a
related substrate. Proton and hydride transfer reactions win be
distinguished by use of deuterium or tritium-labelled compounds.
Catalysis by general acids and metal ions will also be studied. (2) It is
not known whether the glycosyl transfer reactions catalyzed by
beta-galactosidase proceed by a mechanism with discrete chemical steps
for every change in bonding, or by a concerted mechanism where two or
more changes in bonding occur in a single step. These distinctions are
necessary for the definition of the roles of the catalytically essential
amino acid residues Glu-461 and Tyr-503. Stepwise and concerted
mechanisms for the addition of nucleophiles to the galactosyl-enzyme
intermediate (E-Gal) will be distinguished in a study of the reactions of
nucleophilic anions. Stepwise and concerted mechanisms for general
base-catalyzed cleavage of the acylal linkage will be distinguished by a
determination of the effect of changing the basicity of the nucleophile
on the reactivity of E-Gal toward alkyl alcohols and phenols, and the
solvent deuterium isotope effects on these reactions. The transition
state for the general base-catalyzed reaction will be characterized on a
two-dimensional reaction coordinate profile. (3) The barrier for the
addition reaction of an enolate ion to a carbonyl group in water will be
determined, in order to assess whether it is advantageous for enzyme
catalysts (e.g., aldolases) to stabilize the transition state for this
reaction. The effectiveness of buffer acids as catalysts of addition of
enolates to the carbonyl group will also be determined.
It has been demonstrated on numerous occasions that studies on enzyme
mechanisms may provide information critical for drug design (enzyme
inhibitors), to the understanding metabolic diseases, and to the
resolution of other health-related problems.
提出了与该机制直接相关的几个问题
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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John P Richard其他文献
John P Richard的其他文献
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{{ truncateString('John P Richard', 18)}}的其他基金
Studies on Enzyme Activation and Novel Modes of Inhibition
酶激活和新抑制模式的研究
- 批准号:
10317064 - 财政年份:2020
- 资助金额:
$ 14.06万 - 项目类别:
Studies on Enzyme Activation and Novel Modes of Inhibition
酶激活和新抑制模式的研究
- 批准号:
10543563 - 财政年份:2020
- 资助金额:
$ 14.06万 - 项目类别:
Activation of Enzymes for Catalysis: The Role of Substrate-Induced Structural Changes
催化酶的激活:底物诱导的结构变化的作用
- 批准号:
9198549 - 财政年份:2016
- 资助金额:
$ 14.06万 - 项目类别:
MECHANISMS FOR ENZYME CATALYSIS OF HETEROLYTIC REACTIONS
酶催化杂解反应的机制
- 批准号:
3306774 - 财政年份:1992
- 资助金额:
$ 14.06万 - 项目类别:
MECHANISMS FOR ENZYME CATALYSIS OF HETEROLYTIC REACTION
酶催化杂解反应的机理
- 批准号:
3306775 - 财政年份:1992
- 资助金额:
$ 14.06万 - 项目类别:
MECHANISMS FOR ENZYME CATALYSIS OF HETEROLYTIC REACTION
酶催化杂解反应的机理
- 批准号:
2184726 - 财政年份:1992
- 资助金额:
$ 14.06万 - 项目类别:
MECHANISMS FOR ENZYME CATALYSIS OF HETEROLYTIC REACTION
酶催化杂解反应的机理
- 批准号:
2184725 - 财政年份:1992
- 资助金额:
$ 14.06万 - 项目类别:
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