Crystal structure of the tyrosine kinase domain of the human insulin receptor.
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.
Hubbard
S R
SR
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032.
Wei
L
L
Ellis
L
L
Hendrickson
W A
WA
D000595:Amino Acid Sequence; D001665:Binding Sites; D003196:Computer Graphics; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011487:Protein Conformation; D011972:Receptor, Insulin / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins; D013379:Substrate Specificity; D014443:Tyrosine / Q000378:metabolism
D011994:Recombinant Proteins; D014443:Tyrosine; D011972:Receptor, Insulin