STRUCTURE-FUNCTION STUDIES OF DNA BINDING PROTEINS AND ENZYMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本文描述的研究旨在更深入地了解几类DNA结合蛋白和酶的结构与功能关系。目前，实验室中有五个项目已经产生了需要同步加速器光束时间的晶体：(1)II型限制性内切酶间接读出的作用，(2)二价阳离子依赖核酸酶切割DNA的立体化学切割机制，(3)四聚体II型限制性内切酶的特异性调节，(4)DNA修复蛋白对受损DNA的识别，(5)人工C2H2锌指的识别密码。许多研究涉及蛋白质和酶如何实现非常高的DNA序列辨别力。酶机制在一个模型系统中研究DNA切割的机制，这被认为与许多医学上相关的人类核酸内切酶有许多共同之处。DNA修复蛋白在细胞功能中起着重要的作用，可以识别启动修复过程的损伤，也可以决定细胞的命运，细胞的死亡可以是修复或程序性死亡。锌手指项目是与加州大学戴维斯分校的大卫·西格尔教授和斯克里普斯研究所的卡洛斯·巴巴斯教授的实验室合作的，他们正在努力创造新的疗法来识别和治疗癌症和艾滋病等疾病。

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. The studies described herein aim to gain a deeper understanding of structure-function relationships in several classes of DNA binding proteins and enzymes. Currently, five projects in the lab have generated crystals requiring synchrotron beamtime: (1) the role of indirect readout by type II restriction endonucleases, (2) the stereochemical cleavage mechanism of DNA cleavage by divalent cation dependent nucleases, (3) the modulation of specificity in a tetrameric type II restriction endonuclease, (4) the recognition of damaged DNA by DNA repair proteins, (5) the recognition code of artificial C2H2 zinc fingers. Many involve the investigation of how proteins and enzymes achieve very high DNA sequence discrimination. The enzymatic mechanisms study the mechanism of DNA cleavage in a model system, which is believed to have much in common with many medically relevant human endonucleases. The DNA repair proteins are important in cellular function in identifying damage for the initiation of the repair process, and also for decision making regarding the cell fate, which can be either repair or programmed cell death. The zinc finger project is in collaboration with the laboratories of Prof. David Segal, UC Davis, and Prof. Carlos Barbas, Scripps Institute, where efforts are under way to create new therapeutics for the identification and treatment of diseases such as cancer and AIDS.