Atom-specific Selenium Derivatization of Nucleic Acids for Crystallization and Structure Studies

用于结晶和结构研究的核酸原子特异性硒衍生化

• 批准号: 0824837
• 负责人: Zhen Huang
• 金额: $ 84.73万
• 依托单位: Georgia State University Research Foundation, Inc.
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0824837&HistoricalAwards=false
• 关键词: Atom; specific; Selenium; Derivatization; Nucleic

Intellectual Merit: X-ray crystallography is one of the best methods for the determination and study of 3-D structures of nucleic acids and protein-nucleic acid complexes at the atomic level. Such studies provide novel insights into nucleic acid functions and mechanisms. Via atom-specific substitution of nucleic acid oxygen with selenium, the research group on this project has pioneered and developed the selenium modification for nucleic acid heavy atom derivatization and crystallization, which are the two major challenges/bottlenecks in nucleic acid X-ray crystallography. This project has led to a successful demonstration of the utility of selenium derivatization for phasing, and to the discovery of crystallization facilitation by the 2'-Se derivatization of nucleic acids. The current research project involves further X-ray crystallographic studies on DNAs and RNAs in order to provide a viable rational solution for standard heavy atom derivatization and phase determination, as well as a potential solution for crystallization facilitation. The intellectual merit of this research project is in providing new insights into molecular interactions, packing, crystallization mechanisms, crystal growth facilitation, as well as structures of the Se-derivatized DNAs and RNAs and the corresponding natural nucleic acids. In addition, new synthetic routes to introduce Se into multiple positions of DNAs and RNAs will be developed for function and crystal structure studies. Broader Impact of the Research: This research project will significantly enlarge scientific knowledge on nucleic acids, lead to novel materials and applications, allow broader access to these valuable new materials and unique molecules, as well as attract the attention of the general public. This research group will reach out to faculty members in research non-intensive colleges and high schools, and invite them to participate in this research project. The outreach and research opportunities will help to raise the awareness and scientific literacy of the general public. Moreover, many students, especially underrepresented minority students, will be trained through participation in this project in hands-on experimental research, and scientific communication skills. The Chemistry Department at Georgia State University (GSU) has a strong tradition of educating and serving undergraduate and graduate students, especially underrepresented minority students. This project will offer various extensive multi-disciplinary training opportunities and generate synergy in research training in both Chemistry and Biology Departments at GSU.

智力优点：X射线晶体学是对原子水平上核酸和蛋白质核酸络合物的3-D结构进行测定和研究的最佳方法之一。这样的研究提供了对核酸功能和机制的新见解。该项目的研究小组通过原子特异性取代了核酸氧的取代，并开发了核酸重原子衍生化和结晶的硒修饰，这是核酸X射线晶体学的两个主要挑战/瓶颈。该项目已成功证明了硒衍生物对相位的实用性，并通过2'-SE衍生化的核酸衍生化发现了结晶的促进。当前的研究项目涉及对DNA和RNA的进一步X射线晶体学研究，以便为标准的重原子衍生化和相确定提供可行的合理解决方案，以及用于结晶促进的潜在解决方案。该研究项目的智力优点在于为分子相互作用，包装，结晶机制，晶体生长促进以及SEDERIVATIAL DNA和RNA的结构以及相应的天然核酸提供新的见解。此外，将开发用于将SE引入DNA和RNA多个位置的新合成途径用于功能和晶体结构研究。 研究的更广泛影响：该研究项目将大大扩大有关核酸的科学知识，导致新颖的材料和应用，从而更广泛地使用这些有价值的新材料和独特的分子，并引起公众的关注。该研究小组将与研究非密集型大学和高中的教职员工接触，并邀请他们参加该研究项目。宣传和研究机会将有助于提高公众的意识和科学素养。此外，许多学生，尤其是代表性不足的少数族裔学生，将通过参加该项目的实验性研究和科学沟通技巧来接受培训。佐治亚州立大学（GSU）的化学系具有扎实的传统，即教育和服务本科生和研究生，尤其是代表性不足的少数民族学生。该项目将提供各种广泛的多学科培训机会，并在GSU的化学和生物学部门的研究培训中产生协同作用。