Minority Postdoctoral Research Fellowships in Biological Sciences for FY 2000

本行动资助美国国家科学基金会2000年度少数民族生物科学博士后研究奖学金。这项研究和培训计划是在生物物理学领域，名为“模型蛋白质的蛋白质工程”。本研究使用合成的二铁氧蛋白（DF）作为金属蛋白类的模型，这些金属蛋白在生命系统中具有多种功能，包括二氧运输、核糖核苷酸向脱氧核糖核苷酸的转化、脂肪酸的去饱和以及铁的溶解和储存。DF被设计为二铁氧蛋白的最小模型，并且已被证明含有与二铁氧蛋白非常相似的金属中心。这个模型很有趣，因为所有二铁氧蛋白中的双核金属中心都包含许多共同的结构特征，但同时又包含细微的差异，从而产生不同的活性。这使得二铁氧系统对研究蛋白质环境如何影响活性位点功能具有吸引力。该项目旨在将第一代DF系统改进为可用于工程和设计工作的系统，并通过以下方式研究二铁氧蛋白功能：(1)开发一种高效的DF合成方法，这将提供一种快速生成大量DF变体的方法；(2)通过系统地改变活性位点附近的原子来研究中心功能和结构的决定因素。完成这些目标将指导在二铁-氧中心设计预定义功能的努力。

This action funds an NSF Minority Postdoctoral Research Fellowship in Biological Sciences for FY 2000.The research and training plan is in the area of biophysics and is entitled "Protein Engineering of a Model Protein." This study uses a synthetic diiron-oxo protein (DF) as a model for the class of metalloproteins that performs a variety of functions in living systems including dioxygen transport, conversion of ribonucleotides to deoxyribonucleotides, desaturation of fatty acids, and the solubilization and storage of iron. DF has been designed to serve as a minimal model of diiron-oxo proteins and has been shown to contain a metal center that is very similar to the diiron-oxo proteins. The model is interesting because the dinuclear metal centers in all diiron-oxo proteins contain many common structural features, but at the same time contain subtle differences that give rise to different activities. This makes the diiron-oxo system attractive for studying how protein environments can influence active site functions. This projects seeks to refine the first generation DF system into one that is amenable for engineering and designing efforts and for studying diiron-oxo protein function by (1) developing an efficient synthesis of DF which would offer a quick way to generate large numbers of DF variants and (2) by investigating the determinants for the function and structure of the center by systematically altering the atoms near the active site. Completing these goals will guide efforts towards designing pre-defined functions into the diiron-oxo centers.