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Three-dimensional structure of the Hck SH2 domain in solution

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Abstract

The hematopoietic cellular kinase (Hck) is a member of the Srcfamily of non-receptor protein-tyrosine kinases that is expressedpredominantly in granulocytes, monocytes and macrophages. Recentobservations suggest that Hck may be activated in HIV-infected macrophagesand in chronic myelogenous leukemia cells that express Bcr-Abl. In order toincrease our understanding of the structural basis for regulation of Hckactivity under normal and pathological conditions, we have solved thesolution structure of the uncomplexed Hck SH2 domain using NMR spectroscopy.A novel procedure that uses intraresidueHN™Hα distances as references forconverting NOE intensities into distance restraints has been described. Atotal of 1757 significant experimental restraints were derived from NMRspectroscopic data including 238 medium-range and 487 long-range distancerestraints and 177 torsion angle restraints. These restraints were used in asimulated annealing procedure to generate 20 structures with the programDYANA. Superimposition of residues 5–104 upon the mean coordinate setyielded an average atomic rmsd values of 0.42 ± 0.08 Å for theN,Cα,C′ atoms and 0.81 ± 0.08 Å forall heavy atoms. Rmsd values for those residues in the regions of orderedsecondary structure were 0.27 ± 0.04 Å for theN,Cα,C′ atoms and 0.73 ± 0.06 Å forall heavy atoms.

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Authors and Affiliations

  1. The Eppley Institute for Research in Cancer and Allied Diseases, The University of Nebraska Medical Center, Omaha, NE, 68198-6805, U.S.A

    Weixing Zhang, Thomas E. Smithgall & William H. Gmeiner

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  1. Weixing Zhang
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  2. Thomas E. Smithgall
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Zhang, W., Smithgall, T.E. & Gmeiner, W.H. Three-dimensional structure of the Hck SH2 domain in solution. J Biomol NMR 10, 263–272 (1997). https://doi.org/10.1023/A:1018386217930

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