Abstract

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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-20
Application #
6667809
Study Section
Project Start
2002-09-30
Project End
2003-08-14
Budget Start
Budget End
Support Year
20
Fiscal Year
2002
Total Cost
$142,703
Indirect Cost

  Institution

Name
Cornell University
Department
Type
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Xu, Jie; Kozlov, Guennadi; McPherson, Peter S et al. (2018) A PH-like domain of the Rab12 guanine nucleotide exchange factor DENND3 binds actin and is required for autophagy. J Biol Chem 293:4566-4574
Dean, Dexter N; Rana, Pratip; Campbell, Ryan P et al. (2018) Propagation of an A? Dodecamer Strain Involves a Three-Step Mechanism and a Key Intermediate. Biophys J 114:539-549
Chen, Yu Seby; Kozlov, Guennadi; Fakih, Rayan et al. (2018) The cyclic nucleotide-binding homology domain of the integral membrane protein CNNM mediates dimerization and is required for Mg2+ efflux activity. J Biol Chem 293:19998-20007
Kozlov, Guennadi; Wong, Kathy; Gehring, Kalle (2018) Crystal structure of the Legionella effector Lem22. Proteins 86:263-267
Ménade, Marie; Kozlov, Guennadi; Trempe, Jean-François et al. (2018) Structures of ubiquitin-like (Ubl) and Hsp90-like domains of sacsin provide insight into pathological mutations. J Biol Chem 293:12832-12842
Xu, Caishuang; Kozlov, Guennadi; Wong, Kathy et al. (2016) Crystal Structure of the Salmonella Typhimurium Effector GtgE. PLoS One 11:e0166643
Cogliati, Massimo; Zani, Alberto; Rickerts, Volker et al. (2016) Multilocus sequence typing analysis reveals that Cryptococcus neoformans var. neoformans is a recombinant population. Fungal Genet Biol 87:22-9
Oot, Rebecca A; Kane, Patricia M; Berry, Edward A et al. (2016) Crystal structure of yeast V1-ATPase in the autoinhibited state. EMBO J 35:1694-706
Lucido, Michael J; Orlando, Benjamin J; Vecchio, Alex J et al. (2016) Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. Biochemistry 55:1226-38
Bauman, Joseph D; Harrison, Jerry Joe E K; Arnold, Eddy (2016) Rapid experimental SAD phasing and hot-spot identification with halogenated fragments. IUCrJ 3:51-60

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