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Crystal structure of the tyrosine kinase domain of the human insulin receptor

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Abstract

The X-ray crystal structure of the tyrosine kinase domain of the human insulin receptor has been determined by multiwavelength anomalous diffraction phasing and refined to 2.1 Å resolution. The structure reveals the determinants of substrate preference for tyrosine rather than serine or threonine and a novel autoinhibition mechanism whereby one of the tyrosines that is autophosphorylated in response to insulin, Tyr 1,162, is bound in the active site.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, 10032, USA

    Stevan R. Hubbard & Wayne A. Hendrickson

  2. Howard Hughes Medical Institute, Columbia University, New York, New York, 10032, USA

    Wayne A. Hendrickson

  3. W. M. Keck Center for Genome Informatics, Institute of Biosciences and Technology, Texas A & M University, Houston, Texas, 77030, USA

    Lei Wei

Authors
  1. Stevan R. Hubbard
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  2. Lei Wei
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  3. Wayne A. Hendrickson
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Hubbard, S., Wei, L. & Hendrickson, W. Crystal structure of the tyrosine kinase domain of the human insulin receptor. Nature 372, 746–754 (1994). https://doi.org/10.1038/372746a0

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