核磁共振波谱学在生物分析与有机分析中应用.pdfVIP

A018 核磁共振波谱学在生物分析与有机分析中应用 曹春阳 中国科学院上海有机化学研究所生命有机国家重点实验室， 上海市零陵路345 号， 200032 基于核磁共振波谱学，并结合X-ray ，荧光光谱，等温滴定技术(ITC)、圆二色谱、有机 合成等技术，开展具有重要生物功能的蛋白质与核酸结构与功能关系研究，复杂的生物大 分子相互识别机制研究, 以及蛋白质高效制备新方法研究。(1)拆分手性的骨架磷硫修饰的 DNA ，利用NMR 解析磷硫修饰对DNA 结构与功能影响；(2) 发现与乳腺癌发生过程相关 的UHRF1 蛋白PHD 结构域能特异性识别组蛋白N-端未修饰H3R2 位点，而不是H3K9me3 位点；PLU1 蛋白的PHD1 结构域通过识别组蛋白H3K4me0 肽段调控PLU1 蛋白去组蛋白 甲基化活性，从而调控乳腺癌细胞的发育；(3) 确定了肿瘤因子RET 蛋白富含GC 碱基启 动子区的G- 四联体DNA 溶液结构，发现该结构包含一个全新的全是顺式构象的G4 聚体 平面；(4) 开发了基于NMR 与CD 谱学的多锌指蛋白可溶性表达新方法。 同时将展示基于NMR 波谱学的、针对有机小分析结构解析多种技巧。 NMR studies application in biological or organic analysis Chunyang Cao State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, CAS, 345 Lingling Road, Shanghai, 200032, China Research interests in my lab are mainly focused on studies about the relationship between the structures and the functions of key proteins and nucleic acids, the structural basis for their specific interaction, and the development of the methods for protein soluble expression or effiently refolding, by nuclear magnetic resonance (NMR), X-ray, fluorescence spectroscopy, isothermal titration calorimetry assay, circular dichroism spectroscopy, organic synthesis and other techniques. The exciting results include: (1) NMR studies on the effects on the structures and functions by DNA phosphorothioation; (2) Structural basis for site-specific readout of unmodified R2 of histone H3 tail (not H3k9me3, as predicted before) by UHRF1 PHD finger; the mechanism of how PLU1-PHD1 functions in histone H3K4me3/me2 demethylation; (3) Solution str