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

这个子项目是许多利用 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。 我的实验室率先并成功地证明了一种新的衍生化策略，通过用硒取代核酸的氧。我们的研究是基于中心假设，硒可以被用来稳定地取代核酸中的氧原子特异性地没有显着的扰动，因为硒和氧是在同一个元素家庭。我们已经成功地证明了核酸的硒衍生化可以用于解决相位问题。此外，我们发现硒衍生化可以促进寡核苷酸结晶。因此，这种硒衍生化策略具有很大的潜力，提供新的解决方案，这两个长期存在的问题：定相和结晶，特别是核酸和蛋白质-核酸复合物。因此，我们的结构研究重点是开发核酸和蛋白质复合物的定相，结晶和晶体结构测定的一般策略。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. 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. 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.