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

Nature. 1994 Dec 22-29;372(6508):746-54. doi: 10.1038/372746a0.

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 A 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Computer Graphics
  • Conserved Sequence
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics
  • Enzyme Activation
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Protein Conformation
  • Receptor, Insulin / antagonists & inhibitors
  • Receptor, Insulin / chemistry*
  • Receptor, Insulin / metabolism
  • Recombinant Proteins
  • Substrate Specificity
  • Tyrosine / metabolism

Substances

  • Recombinant Proteins
  • Tyrosine
  • Receptor, Insulin