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: 8362110
• 负责人: Nancy C Horton
• 金额: $ 0.25万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362110
• 关键词: 3' -nuclease; Acquired Immunodeficiency Syndrome; Apoptosis; Biological Models; C2H2 Zinc Finger; Cell physiology; Cells; Code; Collaborations; DNA; DNA Damage; DNA Sequence; DNA repair protein; DNA-Binding Proteins; Decision Making; Discrimination; Disease; Divalent Cations; Enzymes; Funding; Grant; Human; Institutes; Investigation; Laboratories; Malignant Neoplasms; National Center for Research Resources; Principal Investigator; Process; Proteins; Radiation; Research; Research Infrastructure; Resources; Role; Source; Specificity; Structure; Structure-Activity Relationship; Synchrotrons; Type II site-specific deoxyribonuclease; United States National Institutes of Health; Zinc Fingers; cost; endonuclease; novel therapeutics; repaired; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 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-功能关系。 目前，实验室的五个项目已生成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特异性的调节，(4) 通过二价限制性内切酶识别受损 DNA DNA修复蛋白，(5)人工C2H2锌指的识别码。 许多涉及蛋白质和酶如何实现非常高的 DNA 序列辨别力的研究。 酶促机制研究模型系统中 DNA 切割的机制，该机制被认为与许多医学相关的人类核酸内切酶有很多共同点。 DNA 修复蛋白在细胞功能中非常重要，可以识别损伤以启动修复过程，并且对于细胞命运（可以是修复或程序性细胞死亡）的决策也很重要。 锌指项目是与加州大学戴维斯分校的 David Segal 教授和斯克里普斯研究所的 Carlos Barbas 教授的实验室合作进行的，该实验室正在努力开发新的疗法来识别和治疗癌症和艾滋病等疾病。