Abstract
FKBP12.6 is a novel isoform of FKBP12, which selectively binds to the cardiac ryanodine receptor (RyR2). The crystal structure of FKBP12.6 in complex with rapamycin has now been determined at 2.0 A resolution. The structures of FKBP12.6 and FKBP12 are nearly identical, except for a displacement observed in the helical region of FKBP12.6 toward the hydrophobic pocket. This displacement was not predicted by homology modeling studies. Analyses of the residues that are likely to confer the RyR2-binding specificity are presented.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Crystallography, X-Ray
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Humans
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Immunophilins / chemistry*
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Immunophilins / metabolism
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Macromolecular Substances
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Models, Molecular
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Molecular Sequence Data
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Protein Binding
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Protein Conformation
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Ryanodine Receptor Calcium Release Channel / metabolism
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Sequence Alignment
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Sequence Homology, Amino Acid
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Sirolimus / chemistry*
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Sirolimus / metabolism
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Tacrolimus Binding Proteins
Substances
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Macromolecular Substances
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Ryanodine Receptor Calcium Release Channel
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Tacrolimus Binding Proteins
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Immunophilins
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Sirolimus