STRUCTURE-FUNCTION STUDIES OF DNA BINDING PROTEINS AND ENZYMES

DNA 结合蛋白和酶的结构功能研究

• 批准号: 7721959
• 负责人: Nancy C Horton
• 金额: $ 0.31万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7721959
• 关键词: 3' -nuclease; Apoptosis; Binding Proteins; Biological Models; C2H2 Zinc Finger; Cell physiology; Cells; Class; Code; Collaborations; Computer Retrieval of Information on Scientific Projects Database; DNA; DNA Damage; DNA Sequence; DNA repair protein; DNA-Binding Proteins; Decision Making; Depth; Discrimination; Disease; Divalent Cations; Enzymes; Funding; Grant; Human; Institutes; Institution; Investigation; Laboratories; Malignant Neoplasms; Process; Proteins; Research; Research Personnel; Resources; Role; Source; Specificity; Structure; Structure-Activity Relationship; Synchrotrons; Type II site-specific deoxyribonuclease; United States National Institutes of Health; Zinc Fingers; endonuclease; novel therapeutics; repaired

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.

这个子项目是许多研究子项目中的一个 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。 本文所述的研究旨在更深入地了解几类DNA结合蛋白和酶的结构-功能关系。 目前，实验室中的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型限制性内切核酸酶间接读出的作用，（2）二价阳离子依赖性核酸酶切割DNA的立体化学切割机制，（3）四聚体II型限制性内切核酸酶中特异性的调节，（4）DNA修复蛋白对受损DNA的识别，（5）人工C_2H_2锌指的识别密码。 许多涉及蛋白质和酶如何实现非常高的DNA序列识别的研究。 酶机制研究模型系统中的DNA切割机制，这被认为与许多医学相关的人类核酸内切酶有很多共同之处。 DNA修复蛋白在细胞功能中是重要的，在识别损伤以启动修复过程中，也用于关于细胞命运的决策，其可以是修复或程序性细胞死亡。 锌指项目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，正在努力创造用于识别和治疗癌症等疾病的新疗法。