STRUCTURAL STUDIES ON THE MLL SET DOMAIN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 组蛋白甲基转移酶由一类称为SET结构域的蛋白质控制，该结构域普遍存在于各种染色质相关蛋白中，包括杂色抑制蛋白、ZEST增强子和三胸蛋白。根据序列同源性，SET结构域可分为五类：SUV39、SET1、Set2、RIZ和Set7/9组。到目前为止，已经确定了SUV39和SET7/9组的成员的结构信息，但目前不存在SET1、SET2和RIZ组的成员的结构信息。我们工作的主要目标是确定来自人类混合血统白血病(MLL)蛋白的SET1类SET结构域的一个成员的三维结构。 在悬滴蒸汽扩散实验中，我们得到了MLL SET区(~18 kDa)板状和棒状晶体，晶体尺寸为300×100×10微米。这些晶体在我们自己的光源上衍射到了~3.0A的分辨率，这是一台带CCD探测器的牛津衍射仪Xcalbur PX-Ultra衍射仪。我们希望使用F1光束线收集高分辨率的数据，这些数据将被用来通过分子置换来确定结构。

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. Histone methyltransferases are dominated by a class of proteins called SET domains, a domain commonly found in a variety of chromatin associated proteins, including Suppressor of Variegation, enhancer of Zest, and Trithorax proteins. SET domains can be divided into five classes based on sequence homology; the SUV39, SET1, SET2, RIZ, and SET7/9 groups. Thus far structural information has been determined for members of the SUV39 and SET7/9 groups, but no structural information currently exists for members of the SET1, SET2, and RIZ groups. The main goal of our work is to determine the three-dimensional structure of a member of the SET1 class of SET domains derived from the human Mixed Lineage Leukemia (MLL) protein. We have obtained MLL SET domain (~18kDa) plate and rod shaped crystals in hanging drop vapor diffusion experiments, with crystal dimensions of 300x 100x10 microns. These crystals diffract to a resolution of ~3.0A on our home source, which is an oxford Diffraction xcalibur PX-Ultra diffractometer with CCD detector. We hope to use the F1 beamline to collect high resolution data which will be used to determine the structure by molecular replacement.