SELENIUM-DERIVATIZED NUCLEIC ACIDS (SENA) FOR PHASING, CRYSTALLIZATION AND X-RAY

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我的实验室开创并成功地展示了一种新的衍生化策略，即用硒取代核酸中的氧。我们的研究是基于中枢假设，即硒可以稳定地取代核酸原子中的氧--具体地说，没有明显的扰动，因为硒和氧属于同一元素家族。我们已经成功地证明了核酸的硒衍生化可以用来解决相问题。此外，我们还发现，硒的衍生化可以促进寡核苷酸的结晶。因此，这种硒衍生化策略具有巨大的潜力，可以为长期存在的问题提供新的解决方案：定相和结晶，特别是对于核酸和蛋白质-核酸复合体。因此，我们的结构研究重点是开发核酸和蛋白质复合体的定相、结晶和晶体结构确定的一般策略。

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. My laboratory pioneered and successfully demonstrated a novel derivatization strategy via replacement of oxygen of nucleic acids with selenium. Our research is based on the central hypothe selenium can be used to stably replace oxygen of nucleic acids atom-specifically without significant perturbation, because selenium and oxygen are in the same elemental family. We have successfully demonstrated that the selenium derivatization of nucleic acids can be useful to solve the phase problem. Moreover, we have found that the selenium derivatization can facilitate oligonucleotide crystallization. Thus, this Se-derivatization strategy has great potential to provide novel solutions to both long-standing problems: phasing and crystallization, especially for nucleic acids and protein-nucleic acid complexes. Therefore, our structural research focuses on developing general strategies for phasing, crystallization, and crystal structure determination of nucleic acids and protein complexes.