X-RAY ABSORPTION STUDIES OF MUTANTS OF COPPER/ZINC SUPEROXIDE DISMUTASE

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 利用X射线吸收光谱（XAS）对一系列铜锌超氧化物歧化酶（CuZnSOD）突变体进行了研究。这些突变体都表现出SOD活性的降低，并且还显示氧化酶的EPR和UV-vis光谱的扰动。铜（II）K-边XAS将允许进一步表征氧化酶的电子和几何结构。Cu（I）K边XAS将允许还原酶的表征，这将有助于理解这些突变体中机制的任何改变。Zn K边XAS将用于确定结构Zn位点是否发生任何变化。这些结果将与WT酶的XAS研究进行比较，并可能为肌萎缩侧索硬化症（ALS）中突变SOD 1酶毒性提供重要见解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. X-ray absorption spectroscopy (XAS) will be used to investigate a series of copper-zinc superoxide dismutase (CuZnSOD) mutants. These mutants all exhibit a decrease in SOD activity and also show perturbations in the EPR and UV-vis spectra of the oxidized enzymes. Cu(II) K-edge XAS will allow for further characterization of the electronic and geometric structure of the oxidized enzyme. Cu(I) K-edge XAS will allow for characterization of the reduced enzyme, which will aid in understanding any alteration in the mechanism in these mutants. Zn K-edge XAS will be used to determine if any changes have occurred at the structural Zn site. These results will be compared to XAS studies on the WT enzyme and may provide important insight into mutant SOD1 enzyme toxicity in amyotrophic lateral sclerosis (ALS).