SYNTHETIC ANALOGS FOR METAL CYSTEINE CONTAINING PROTEINS

含有金属半胱氨酸的蛋白质的合成类似物

• 批准号: 2178292
• 负责人: MICHELLE M. MILLAR
• 金额: $ 17.9万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2178292
• 关键词: Mossbauer spectrometry; X ray crystallography; alkynes; analog; carbon monoxide; chemical reaction; chemical synthesis; cysteine; electrochemistry; electron spin resonance spectroscopy; hydrogen bond; hydrogenase; intermolecular interaction; metal complex; metalloproteins; nickel; nitric oxide; nuclear magnetic resonance spectroscopy; oxidation reduction reaction; thiols

The long-term research objective is to synthesize and fully characterize new types of metal-thiolate complexes for the purpose of obtaining fundamental information about the structural, spectroscopic and reactivity properties of metal-cysteine interactions in proteins. It is proposed that synthetic analogs be acquired and studied as models for the nickel-sulfur and iron-sulfur centers in the hydrogenase (H2-ase) enzymes which catalyze the reversible formation and consumption of dihydrogen (H2) via the redox reaction: 2 H+ + 2 e-H2. Beyond being significant in terms of microbial metabolism, the area of H2 production and consumption from renewable resources is important in the realm of the global energy supply. Although substantial discoveries have been made regarding the biochemistry of the H2-ase enzymes, the exact nature o the active site is not understood. This is an area where fundamental inorganic coordination chemistry can contribute to the understanding of how metal-sulfur centers can catalyze the 2 H+ + 2 e- H2 transformation. It proposed that polydentate chelate ligands be used to prepare metal complexes that replicate the physical and reactivity properties of the metal centers in the H2-ase enzymes. Attention will be given to the synthesis and characterization of Ni complexes which are analogs for the detected forms of the Ni center (Ni-A; Ni-B; Ni-silent; Ni-C) as well as for Ni-hydrogen species that might occur as intermediates in the catalytic cycle. Plans are given which will allow for the synthesis of metal centers in a variety of biologically viable coordination structures and oxidation states [Ni(+n); n = 1,2,3,4]. Chemico-physical studies of the model compounds will be used to obtain a fundamental understanding of the relationship between the spectroscopic and structural and electronic properties of the metal centers. These techniques will include: X-ray crystallography, electrochemical, magnetic susceptibility, electronic, ESR, vibrational, NMR, EXAFS and Mossbauer measurements. Special consideration will be given to understanding the reactivity properties of the H2-ase enzymes. An understanding of the mechanism by which the metal center effects the oxidation of H2 and the reduction of H+ will be sought. It is proposed that the reactivity properties of the metal center can be tuned by modifying the electronic and structural characteristics of the metal-coordination environment. Substantial results have been acquired which suggest that these goals can be achieved. It is anticipated that this work will contribute to understanding the fundamental chemistry and redox-active processes in H2- ase as well as to the chemistry of other biologically relevant metal- cysteine centers.

长期研究目标是合成和充分表征 新型的金属硫醇酸盐络合物，目的 有关结构，光谱和 蛋白质中金属半胱氨酸相互作用的反应性特性。 这是 提议获取并研究合成类似物作为模型 氢化酶（H2-酶）酶中的镍硫和铁硫中心 催化二氢的可逆形成和消耗 （H2）通过氧化还原反应：2 H + + 2 E-H2。 不仅仅是重要 在微生物代谢方面，H2产生和 可再生资源的消费在领域很重要 全球能源供应。 尽管已经发现了大量发现 关于H2-酶酶的生物化学，确切的性质 活跃的站点不了解。 这是一个基本的领域 无机协调化学可以有助于理解 金属硫中心如何催化2 H + + 2 E-H2转化。 它提出了多脱牙螯合剂配体制备金属 复制复制物理和反应性特性的复合物 金属中心在H2-ase酶中。 注意 Ni复合物的合成和表征，这是类似物的类似物 检测的NI中心（NI-A; Ni-B; Ni-SiLent; Ni-C）以及 对于可能作为中间体发生的Ni-Hydrogen物种 催化循环。 给出了计划，该计划将允许合成 金属中心以各种生物学可行的配位结构 和氧化状态[ni（+n）; n = 1,2,3,4]。 化学研究 模型化合物将用于获得基本的理解 光谱与结构与结构之间的关系 金属中心的电子特性。 这些技术会 包括：X射线晶体学，电化学，磁性 易感性，电子，ESR，振动，NMR，EXAFS和Mossbauer 测量。 特殊考虑将是为了理解 H2-ase酶的反应性特性。 对 金属中心影响H2和H2的氧化机制 将寻求减少H+。 有人提出反应性 可以通过修改电子中心的特性来调整电子中心的特性 金属配位环境的结构特征。 已经获得了实质性的结果，这表明这些目标可以 实现。 预计这项工作将有助于 了解H2-中的基本化学和氧化还原活性过程 ASE以及其他与生物学相关的金属的化学 半胱氨酸中心。