Enzyme Structure-Function Relationships
酶结构与功能的关系
基本信息
- 批准号:9418479
- 负责人:
- 金额:$ 33万
- 依托单位:
- 依托单位国家:美国
- 项目类别:Continuing Grant
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-03-01 至 1998-02-28
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
9418479 Remington X-ray crystallographic and mutagenesis studies will be done on two enzymes, citrate synthase from pig and Azotobacter and serine carboxypeptidase from wheat and yeast. Atomic models for the pig, wheat and yeast enzymes are on hand and have been refined at high resolution . These will be used as the basis for inhibitor binding studies that will probe several aspects for the catalytic mechanism. Inhibitors have been designed that mimic proposed transition states of various steps along the catalytic pathway, so as to provide "snapshots: of enzyme conformations and interactions with substrate along the catalytic pathway. The yeast serine carboxypeptidase has been mutated, resulting in greatly changed substrate specificity, and binding studies with peptide aldehydes should reveal the structural consequences of the mutational change and the molecular basis for substrate specificity. The structure of the Azotobacter enzyme will be determined in order to study how bacterial citrate synthases are allosterically regulated by NADH, and how they differ in structure from the non-allosterically regulated enzyme from pig. The bacterial enzyme will also be used as a vehicle for mutagenesis studies which will be designed to probe the functions of specific active-site amino acid side chains. The impetus for this is that most of many interesting mutants of the pig enzyme that exist cannot be crystallized, so the structural consequences of the mutations are unknown. These projects are expected to shed light on the enzymatic mechanisms for two different families of enzymes. Each enzyme poses significant problems concerning the mechanism of catalysis that remain to be understood. Citrate synthase is the only enzyme of known structure that can form a carbon-carbon bond. The energetics of the initial step in the reaction, the deprotonation of a carbon acid, are not understood. Serine carboxypeptidases are serine proteinases that function optimally at pH 4.0-5.0, unlike the other serine proteinases, and the structural basis for this is also not understood. %% X-ray crystallographic and mutagenesis studies will be done on two enzymes, citrate synthetase from pig and Azotobacter, and serine carboxypeptidase from wheat and yeast. These projects are expected to shed light on the enzymatic mechanisms for the two different families of enzymes. Each enzyme possesses significant problems concerning the mechanism of catalysis that remain to be understood. The structure of the Azotobacter enzyme will be determined in order to study how these bacterial enzymes are regulated and how they differ from the pig enzyme. The bacterial enzyme will also be mutated to probe the function of specific active-site amino acid side chains. The yeast serine carboxypeptidase has been mutated, resulting in greatly changed substrate specificity. Binding studies with substrate analogs should reveal the structural consequences of the mutational change and the molecular basis of substrate specificity. ***
9418479将对两种酶进行雷明顿X射线晶体学和诱变研究,这两种酶是来自猪和固氮菌的柠檬酸合酶和来自小麦和酵母的丝氨酸羧肽酶。 猪、小麦和酵母酶的原子模型已经准备就绪,并已在高分辨率下进行了改进。 这些将被用作抑制剂结合研究的基础,将探测催化机制的几个方面。 抑制剂被设计成模拟催化途径沿着各个步骤的过渡态,从而提供酶构象和沿着与底物相互作用的“快照”。 酵母丝氨酸羧肽酶已发生突变,导致底物特异性发生很大变化,肽醛结合研究应揭示突变变化的结构后果和底物特异性的分子基础。 将确定固氮菌酶的结构,以研究细菌柠檬酸脱氢酶如何受NADH变构调节,以及它们在结构上与来自猪的非变构调节酶有何不同。 细菌酶也将被用作诱变研究的载体,诱变研究将被设计用于探测特定活性位点氨基酸侧链的功能。 这是因为猪酶的许多有趣的突变体中的大多数不能被结晶化,因此突变的结构后果是未知的。 这些项目有望揭示两种不同酶家族的酶机制。 每一种酶都提出了关于催化机制的重要问题,这些问题仍有待理解。 柠檬酸合酶是已知结构的唯一可以形成碳-碳键的酶。 反应初始步骤的能量学,即碳酸的去质子化,还不清楚。 丝氨酸羧肽酶是在pH 4.0-5.0最佳发挥功能的丝氨酸蛋白酶,与其他丝氨酸蛋白酶不同,其结构基础也不清楚。 将对两种酶进行X射线晶体学和诱变研究,这两种酶是来自猪和固氮菌的柠檬酸合成酶和来自小麦和酵母的丝氨酸羧肽酶。这些项目有望揭示两种不同酶家族的酶机制。每一种酶都有关于催化机理的重要问题,这些问题尚待了解。固氮菌酶的结构将被确定,以研究这些细菌酶是如何调节的,以及它们与猪酶的不同之处。细菌酶也将被突变以探测特定活性位点氨基酸侧链的功能。酵母丝氨酸羧肽酶已被突变,导致底物特异性大大改变。底物类似物的结合研究应揭示突变变化的结构后果和底物特异性的分子基础。 ***
项目成果
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Stephen Remington其他文献
A new vision for employment support
- DOI:
10.1016/j.ics.2005.05.117 - 发表时间:
2005-09-01 - 期刊:
- 影响因子:
- 作者:
Stephen Remington - 通讯作者:
Stephen Remington
Stephen Remington的其他文献
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{{ truncateString('Stephen Remington', 18)}}的其他基金
Excited State Proton Transfer in Fluorescent Proteins
荧光蛋白中的激发态质子转移
- 批准号:
1021374 - 财政年份:2010
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
Photodynamics and Maturation of Coral Fluorescent Proteins
珊瑚荧光蛋白的光动力学和成熟
- 批准号:
0417290 - 财政年份:2004
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
Structure-Function in Red and Yellow Fluorescent Proteins
红色和黄色荧光蛋白的结构-功能
- 批准号:
0111053 - 财政年份:2001
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
Enzyme Structure-Function Relationships
酶结构与功能的关系
- 批准号:
9728162 - 财政年份:1998
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
Enzyme Structure-Function Relationships
酶结构与功能的关系
- 批准号:
9118302 - 财政年份:1992
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
Enzyme Structure-Function Relationships
酶结构与功能的关系
- 批准号:
8817438 - 财政年份:1989
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
X-ray Structure of Macromolecular Complexes
大分子配合物的X射线结构
- 批准号:
8517785 - 财政年份:1986
- 资助金额:
$ 33万 - 项目类别:
Continuing Grant
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职业:限制下的蛋白质:揭示空间限制对酶结构、动力学和功能的影响
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