EPR Studies of Copper Dynamics in Doped Biological Crystals

掺杂生物晶体中铜动力学的 EPR 研究

• 批准号: 7062791
• 负责人: MICHAEL J COLANERI
• 金额: $ 9.36万
• 依托单位: COLLEGE AT OLD WESTBURY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7062791
• 关键词: cadmium; chemical kinetics; chemical models; copper; crystallization; electron spin resonance spectroscopy; glutamates; glycine; histidine; metal complex; metalloproteins; molecular dynamics; protein structure; theophylline

Electron Paramagnetic Resonance (EPR) spectroscopy will be utilized to study dynamic behavior exhibited by copper in crystals of biological models. Knowledge of dynamic processes in these systems gives important insight into the stability of unusual copper coordination like those frequently found in biological macromolecules. Features of the dynamic processes are normally described by a critical temperature, above which motion becomes rapid enough to average out characteristics of individual species, rate(s) of transition, activation energy (ies) and energy differences of the possible states. This project will determine these parameters and in doing so will provide both a qualitative and quantitative understanding of the potential energy surfaces of the metal complex. This leads to a better understanding of the relationship between stability and structure of copper in metalloproteins. The previous lack of suitable copper model systems showing dynamic behavior has been circumvented by the realization in a survey of copper-doped cadmium-crystals that when Cu2+ replaces Cd2+, the copper complex, in all cases, exhibits dynamic behavior. This is most likely the result of the cadmium ion posessing a larger cage of surrounding ligands than the replacing copper ion. Four such model crystal systems have been initially identified, Cu2+-doped into Cd2+-histidine, Cd2+-theophylline, Cd2+-glycylglycine HCl and Cd2+-glutamate, and are proposed here for detailed EPR investigations. The long term objective is to use this information in studies where copper can act as a surrogate in cadmium-binding proteins and in the newly discovered cadmium-dependent carbonic anhydrase.

电子顺磁共振（EPR）光谱将用于研究铜在生物模型晶体中表现出的动态行为。在这些系统中的动态过程的知识提供了重要的洞察不寻常的铜协调的稳定性，如那些经常发现的生物大分子。动态过程的特征通常由临界温度来描述，在该临界温度以上，运动变得足够快，以平均各个物种的特征、转变速率、活化能和可能状态的能量差。这个项目将确定这些参数，并在这样做将提供一个定性和定量的了解势能面的金属络合物。这导致更好地理解金属蛋白中铜的稳定性和结构之间的关系。以前缺乏合适的铜模型系统 在对铜掺杂的镉晶体的调查中发现，当Cu 2+取代Cd 2+时，铜络合物在所有情况下都表现出动态行为，从而避免了显示动态行为。这很可能是镉离子比取代的铜离子拥有更大的周围配体笼的结果。已初步确定了四个这样的模型晶体系统，Cu~（2+）掺杂到Cd~（2+）-组氨酸、Cd~（2+）-茶碱、Cd~（2+）-甘氨酰甘氨酸盐酸盐和Cd~（2+）-谷氨酸盐中，并在此提出了详细的EPR 调查事务所长期的目标是使用这些信息的研究中，铜可以作为镉结合蛋白和新发现的镉依赖性碳酸酐酶的替代品。