3D STRUCT OF ENZYMES INTERACTING W/ NUCLEOTIDES: ESTROGEN BINDING

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Data were collected at MIT from crystals of CHK SH2 and a data set complete to 3Angstroems was obtained. Molecular replacement was attempted but a solution was not found. The most logical path to take now would have been to search for heavy atom derivatives and collect data. Unfortunately at the time our Laboratory was not equipped with an X-ray facility and we were unable to secure more time at an external establishment. We therefore applied for time at F2 in order to get MAD phases or as a contingency to collect heavy atom data. In the limited time we had at CHESS (around 2.5 days or less) we were unable to find suitable cryo-conditions for the crystals and had to resort to collecting data from potential heavy-atom derivatives. Four potential heavy atom data sets were collected at CHESS F2 and we are in the process of using this data to obtain starting phases for the SH2 domain. Small crystals of the SH2 domain complexed with the receptor peptide ERB-B2 which is expressed in mammalian breast cancer cells have also been grown recently and efforts are being directed to increase the size of these crystals. The crystal structure of the complex would be of fundamental importance in understanding the role of CHK in signalling in breast cancer.