STRUCTURAL STUDIES ON THE MLL SET DOMAIN

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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.