Cu Dioxygen Reactivity in Small Molecule Complexes
小分子配合物中的 Cu 分子氧反应性
基本信息
- 批准号:6775247
- 负责人:
- 金额:$ 31.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1994
- 资助国家:美国
- 起止时间:1994-07-01 至 2008-03-31
- 项目状态:已结题
- 来源:
- 关键词:Raman spectrometryX ray crystallographyactive sitescircular magnetic dichroismcopperelectron spin resonance spectroscopyenzyme activityenzyme mechanismferroxidasefree radical oxygengalactose oxidaseironisomerligandsmelaninsmetal complexmetalloenzymemolecular weightmonophenol monooxygenaseoxidation reduction reactionoxidoreductaseoxygen compoundssynthetic enzymethermostability
项目摘要
DESCRIPTION (provided by applicant): The broad and long-term objective of our research is the mechanistic elucidation of key reaction steps of mono- di- and tri-nuclear copper enzymes that activate O2. The methodology used is that of the synthetic analog approach to the active sites of metallobiomolecules, whereby low molecular weight complexes are synthesized and examined at a small molecule level of detail to reveal intrinsic properties uncoupled from the influences of the protein matrix. Synthetic copper complexes can provide mechanistic details of biological reactions if appropriate attention is directed to the ligation environment. Appropriate ligation can elicit particular chemical reactivity while precluding deleterious bimolecular reactions of nascent Cu-O2 intermediates in a homogenous solution. Creation of a mechanistically faithful and a spectroscopically congruent model provides chemical precedent for a particular oxidative mechanism that can be examined at a small molecule level of detail.
. Structural, spectroscopic and reactivity characterization of [(LPDA)Cul(MeCN)]1+-O2 products using simple peralkylated diamine ligands, L PDA, will provide chemical precedence for possible biological Cu-O2 intermediates and spectroscopic benchmarks by which such intermediates may be identified.
. Spectroscopically congruent models of the binuclear copper enzyme tyrosinase display phenolate monooxygenase reactivity similar to the enzyme. Spectroscopic and kinetic studies of trapped reaction intermediates will provide a more complete mechanistic understanding of this reaction that is the first step in melanin production.
. The postulated tyrosinase active oxidant (Cu ll-O2, P) is potentially in equilibrium with an isoelectronic species (Cu Ill- 02, O). Defining the reactivity behavior of each isomer will address an overarching question of whether the 3+ oxidation state of copper is biologically relevant in binuclear copper sites.
. Spectroscopic and functional models of galactose oxidase (GOase) will probe the chemical reactivity of Cuphenoxyl species.
. A structurally defined trinuclear copper complex will be spectroscopically and magnetically characterized for features similar to the native intermediate in the multi-copper oxidase enzymes. Ceruloplasmin, the major copper-containing enzyme in human blood, is a multi-copper oxidase that is involved in the trafficking of iron (ferroxidase activity).
描述(由申请人提供):我们研究的广泛和长期目标是阐明激活O2的单核、双核和三核铜酶的关键反应步骤的机理。所使用的方法是合成的类似物的方法的活性位点的金属生物分子,从而低分子量的复合物的合成和检查在小分子水平的细节,以揭示从蛋白质基质的影响解耦的固有特性。如果适当关注连接环境,合成的铜络合物可以提供生物反应的机理细节。适当的连接可以引发特定的化学反应性,同时排除在均匀溶液中新生Cu-O2中间体的有害双分子反应。创建一个机械忠实和光谱一致的模型提供了一个特定的氧化机制,可以在一个小分子水平的细节检查化学先例。
.结构,光谱和反应特性的[(LPDA)铜(MeCN)]1+-O2产品使用简单的全烷基化二胺配体,L PDA,将提供化学优先级为可能的生物Cu-O2中间体和光谱基准,这些中间体可以被识别。
.双核铜酶酪氨酸酶的光谱全等模型显示酚单加氧酶的反应类似的酶。光谱和动力学研究的捕获反应中间体将提供一个更完整的机制,这是在黑色素生产的第一步反应的理解。
.假定的酪氨酸酶活性氧化剂(Cu II-O2,P)可能与等电子物质(Cu III-O2,O)平衡。定义每种异构体的反应行为将解决一个首要问题,即铜的3+氧化态在双核铜位点中是否具有生物学相关性。
.半乳糖氧化酶(GOase)的光谱和功能模型将探测Cuphenoxyl物种的化学反应性。
.一个结构确定的三核铜配合物将光谱和磁性特征类似的天然中间体的多铜氧化酶。铜蓝蛋白是人体血液中主要的含铜酶,是一种多铜氧化酶,参与铁的运输(铁氧化酶活性)。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
T DANIEL STACK其他文献
T DANIEL STACK的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('T DANIEL STACK', 18)}}的其他基金
Binuclear Copper-O2 Intermediates: Thermodynamic and Mechanistic Insights
双核铜-O2 中间体:热力学和机理见解
- 批准号:
9357623 - 财政年份:2016
- 资助金额:
$ 31.61万 - 项目类别:
Binuclear Copper-O2 Intermediates: Thermodynamic and Mechanistic Insights
双核铜-O2 中间体:热力学和机理见解
- 批准号:
9154469 - 财政年份:2016
- 资助金额:
$ 31.61万 - 项目类别:
OXIDATIVE REACTIVITY IN BIOINSPIRED METAL COMPLEXES
仿生金属络合物的氧化反应性
- 批准号:
7724179 - 财政年份:2008
- 资助金额:
$ 31.61万 - 项目类别:
Cu Dioxygen Reactivity in Small Molecule Complexes
小分子配合物中的 Cu 分子氧反应性
- 批准号:
7216907 - 财政年份:1994
- 资助金额:
$ 31.61万 - 项目类别:
相似海外基金
CHEMICAL SCREENING AND OPTIMIZATION FACILITY - PROTEIN EXPRESSION AND/OR X-RAY CRYSTALLOGRAPHY
化学筛选和优化设施 - 蛋白质表达和/或 X 射线晶体学
- 批准号:
10942884 - 财政年份:2023
- 资助金额:
$ 31.61万 - 项目类别:
Taking Snapshots of Enzymatic Reactions Using X-ray Crystallography and Spectroscopy
使用 X 射线晶体学和光谱学拍摄酶反应快照
- 批准号:
10623717 - 财政年份:2023
- 资助金额:
$ 31.61万 - 项目类别:
EAGER: JOINT CRYO NEUTRON/X-RAY CRYSTALLOGRAPHY OF RNA AND RNA-PROTEIN INTERACTIONS
EAGER:RNA 和 RNA-蛋白质相互作用的联合冷冻中子/X 射线晶体学
- 批准号:
2224897 - 财政年份:2022
- 资助金额:
$ 31.61万 - 项目类别:
Standard Grant
Protein structure-based enhancement of enzyme performance for food and bioproduct applications using X-ray crystallography, protein modification and metabolic engineering methods
使用 X 射线晶体学、蛋白质修饰和代谢工程方法,基于蛋白质结构增强食品和生物产品应用中的酶性能
- 批准号:
RGPIN-2016-06209 - 财政年份:2021
- 资助金额:
$ 31.61万 - 项目类别:
Discovery Grants Program - Individual
Time-Resolved X-ray Crystallography of Dynamics in Cysteine-Dependent Enzymes
半胱氨酸依赖性酶动力学的时间分辨 X 射线晶体学
- 批准号:
10684770 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Time-Resolved X-ray Crystallography of Dynamics in Cysteine-Dependent Enzymes
半胱氨酸依赖性酶动力学的时间分辨 X 射线晶体学
- 批准号:
10259757 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Elucidating the Hidden Steps of Replicative DNA Synthesis by Time-Resolved X-ray Crystallography
通过时间分辨 X 射线晶体学阐明复制 DNA 合成的隐藏步骤
- 批准号:
2001434 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Standard Grant
Time-Resolved X-ray Crystallography of Dynamics in Cysteine-Dependent Enzymes
半胱氨酸依赖性酶动力学的时间分辨 X 射线晶体学
- 批准号:
10099548 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Optimizing protein expression for X-ray crystallography studies and medicinal chemistry
优化 X 射线晶体学研究和药物化学的蛋白质表达
- 批准号:
552236-2020 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
University Undergraduate Student Research Awards
Protein structure-based enhancement of enzyme performance for food and bioproduct applications using X-ray crystallography, protein modification and metabolic engineering methods
使用 X 射线晶体学、蛋白质修饰和代谢工程方法,基于蛋白质结构增强食品和生物产品应用中的酶性能
- 批准号:
RGPIN-2016-06209 - 财政年份:2020
- 资助金额:
$ 31.61万 - 项目类别:
Discovery Grants Program - Individual