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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Computer Graphics
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Conserved Sequence
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Crystallography, X-Ray
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Diabetes Mellitus, Type 2 / enzymology
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Diabetes Mellitus, Type 2 / genetics
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Enzyme Activation
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Humans
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Molecular Sequence Data
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Mutation
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Phosphorylation
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Protein Conformation
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Receptor, Insulin / antagonists & inhibitors
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Receptor, Insulin / chemistry*
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Receptor, Insulin / metabolism
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Recombinant Proteins
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Substrate Specificity
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Tyrosine / metabolism
Substances
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Recombinant Proteins
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Tyrosine
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Receptor, Insulin