REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
基本信息
- 批准号:2701785
- 负责人:
- 金额:$ 20.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-05-01 至 2002-04-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION:Pyridoxal phosphate (PLP) dependent enzymes are ubiquitous in
nitrogen metabolism and catalyze many medically important transformations.
As a group, they catalyze an extraordinarily wide variety of reactions, and
a fundamental, unresolved question that bears on the design of enzyme
inhibitors is how a given apoenzyme determines a unique reaction
specificity. Dialkylglycine decarboxylase (DGD) is an unusual PLP dependent
enzyme that rapidly catalyzes both decarboxylation and transamination in its
normal catalytic cycle, thereby providing a vehicle for incisive studies on
the control of enzymatic reaction specificity. High resolution X-ray
structures for DGD are available, and reveal two alkali metal ion-specific
binding sites. One, near the active site, is responsible for the activating
effects of large (K+, Rb+) and inhibitory effects of small (Na+, Li+) ions.
The elucidation of the mechanisms by which DGD discriminates between and is
catalytically controlled by alkali metals has very broad physiological
significance. DGD is structurally representative of a medically important
class of aminotransferases capable of acting alternately on primary amines
and alpha-amino acids. The specific aims of this project are to test the
hypotheses that: 1) C-C (decarboxylation) and C-H (transamination) bond
cleavage occur via a single substrate binding subsite in the DGD active
site, which activates these bonds by large stereoelectronic effects; 2) DGD
specifically catalyzes oxidative vs. non-oxidative decarboxylation by
proceeding through a concerted transition state in which CO2 loss and proton
transfer occur simultaneously; 3) Active site structural changes in Ser80
and Tyr301 caused by exchange of activating for inhibitory ions control
catalytic activity; 4) The ability of several aminotransferases to act in
alternative half-reactions on primary amines and alpha-amino acids is
largely determined by two active site residues, Glu215 and Va1244.
描述:磷酸吡哆醛(PLP)依赖的酶普遍存在于
氮代谢和催化许多医学上重要的转变。
作为一个基团,它们催化了非常广泛的反应,并且
与酶的设计有关的一个基本的、尚未解决的问题
抑制剂是特定的脱辅酶决定独特反应的方式
专一性。二烷基甘氨酸脱羧酶(DGD)是一种罕见的PLP依赖性酶
一种能快速催化ITS中的脱羧基和转氨基的酶
正常的催化循环,从而为深入研究
酶反应专一性的控制。高分辨率X射线
DGD的结构是可用的,并揭示了两个碱金属离子特有的
结合部位。一个在活性部位附近负责激活
大离子(K+、Rb+)的影响和小离子(Na+、Li+)的抑制作用。
阐明DGD区分和IS的机制
碱金属催化控制具有非常广泛的生理功能
意义。DGD在结构上代表了一种具有重要医学意义的
一类能交替作用于伯胺的氨基转移酶
和α-氨基酸。这个项目的具体目标是测试
假设:1)C-C(脱羧基)和C-H(转氨基)键
在DGD活性中,通过单个底物结合亚位发生切割
Site,通过大的立体电子效应激活这些键;2)DGD
通过以下方式特异性地催化氧化性和非氧化性脱羧基
通过二氧化碳损失和质子的协调过渡状态
转移同时发生;3)Ser80的活动部位结构变化
和Tyr301引起的抑制离子调控的激活交换
催化活性;4)几种氨基转移酶作用于
伯胺和α-氨基酸的替代半反应是
主要由两个活性位点残基Glu215和Va1244决定。
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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Michael Toney其他文献
Michael Toney的其他文献
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{{ truncateString('Michael Toney', 18)}}的其他基金
REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
- 批准号:
6386627 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
- 批准号:
2023526 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
- 批准号:
6181243 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
Reaction Specificity of Pyridoxal Phosphate Enzymes
磷酸吡哆醛酶的反应特异性
- 批准号:
7695551 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
Reaction Specificity of Pyridoxal Phosphate Enzymes
磷酸吡哆醛酶的反应特异性
- 批准号:
8131680 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
- 批准号:
2910277 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
Reaction Specificity of Pyridoxal Phosphate Enzymes
磷酸吡哆醛酶的反应特异性
- 批准号:
7418818 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
Reaction Specificity of Pyridoxal Phosphate Enzymes
磷酸吡哆醛酶的反应特异性
- 批准号:
6579343 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
Reaction Specificity of Pyridoxal Phosphate Enzymes
磷酸吡哆醛酶的反应特异性
- 批准号:
6853518 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
REACTION SPECIFICITY OF PYRIDOXAL PHOSPHATE ENZYMES
磷酸吡哆醛酶的反应特异性
- 批准号:
6569862 - 财政年份:1997
- 资助金额:
$ 20.03万 - 项目类别:
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