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Model Studies of Acetyl Coenzyme A Synthase

乙酰辅酶A合酶的模型研究

基本信息

批准号：
7544968
负责人：
CHARLES G. RIORDAN
金额：
$ 21.55万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-04-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7544968
关键词：
Acetates Acetyl Coenzyme A Active Sites Address Anabolism Architecture Area Bacteria Binding Binding Sites Biochemical Reaction Biological Biological Models Catalysis Catalytic Domain Chemicals Colon Communities Complex Crystallography Electronics Ensure Enzymes Functional disorder Gastric lymphoma Goals Helicobacter pylori Human Individual Inorganic Chemistry Investigation Kinetics Knowledge Laboratories Libraries Measurement Metals Methodology Modeling Molecular Molecular Weight Mononuclear Nickel Organism Oxidation-Reduction Peptic Ulcer Peptides Preparation Production Property Proteins Protocols documentation Reaction Research Research Personnel Scheme Site Stomach Carcinoma Structure Structure-Activity Relationship Study models System Testing Time Toxic effect Trace Elements analog base carcinogenesis chemical property design electronic structure functional group interest novel oxidation programs research study structural biology

项目摘要

The proposed research is designed to address specific questions of molecular and electronic structure, and chemical reactivity to gain a fundamental understanding of the catalytic activity of the Ni-containing protein acetyl coenzyme A synthase (ACS) through the synthesis, characterization and elucidation of reactivity of model complexes. This methodology will permit characterization of the intrinsic properties of structure and function of the metal sites at the molecular level of detail decoupled from the protein architecture. Recent results from structural biology have established details of the active site structure making now the optimum time to address this problem as the targets are well defined. Individual reactions will be systematically interrogated using the protocols of mechanistic inorganic chemistry including product analyses, kinetic measurements, stereochemical and radical clock probe investigations. The long-term goal of this project is to develop a detailed mechanistic understanding of how the structural, electronic and chemical properties of nickel sites in proteins are optimized for their intended catalytic transformations. The proposed research impacts our understanding of the biological implications of the essential trace element nickel that include the virility of Helicobacter pylori which has been associated with peptic ulcer disease, gastric carcinoma, and gastric lymphoma, and carcinogenesis through production of oxidizing species that degrade DMA. Additionally, acetogenic and methanogenic bacteria, organisms that contain ACS, may be important to human digestive function and dysfunction as they occupy a large volume of the colon. More broadly, a deeper understanding of ACS catalysis will advance fundamental understanding of redox-based Ni toxicity.

提出的研究旨在解决分子和电子结构的具体问题，以及

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Synthetic chemistry and chemical precedents for understanding the structure and function of acetyl coenzyme A synthase.

了解乙酰辅酶 A 合酶结构和功能的合成化学和化学先例。

DOI：
10.1007/s00775-004-0567-7
发表时间：
2004
期刊：
Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry
影响因子：
0
作者：
Riordan,CharlesG
通讯作者：
Riordan,CharlesG

Coordination chemistry of poly(thioether)borate ligands.

DOI：
10.1016/j.ccr.2010.01.007
发表时间：
2010-08-01
期刊：
Coordination chemistry reviews
影响因子：
20.6
作者：
Riordan CG
通讯作者：
Riordan CG

Thiolate-bridged nickel-copper complexes: A binuclear model for the catalytic site of acetyl coenzyme A synthase?

DOI：
10.1021/ja0346577
发表时间：
2003-04-16
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Krishnan, R;Voo, JK;Rheingold, AL
通讯作者：
Rheingold, AL

Spectroscopic and computational studies on [Ni(tmc)CH3]OTf: implications for Ni-methyl bonding in the A cluster of acetyl-CoA synthase.

[Ni(tmc)CH3]OTf 的光谱和计算研究：对乙酰辅酶 A 合酶 A 簇中 Ni-甲基键合的影响。

DOI：
10.1021/ic0483996
发表时间：
2005
期刊：
Inorganic chemistry
影响因子：
4.6
作者：
Schenker,Ralph;Mock,MichaelT;Kieber-Emmons,MatthewT;Riordan,CharlesG;Brunold,ThomasC
通讯作者：
Brunold,ThomasC

Binuclear complexes containing a methylnickel moiety: relevance to organonickel intermediates in acetyl coenzyme A synthase catalysis.

DOI：
10.1021/ja803795k
发表时间：
2008-10-15
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Dougherty, William G.;Rangan, Krishnan;O'Hagan, Molly J.;Yap, Glenn P. A.;Riordan, Charles G.
通讯作者：
Riordan, Charles G.