Abstract
The 3D structure of two unlabeled FK506 analogs, (R)- and (S)-[18-OH]ascomycin, when bound to [U-13C,15N]FKBP were determined by isotope-filtered 2D NMR experiments. The structures for the R and S isomers that bind tightly to FKBP but lack immunosuppressive activity are compared to each other and to the conformation of the potent immunosuppressant, ascomycin, when bound to FKBP. The results are interpreted in terms of calcineurin binding to the FKBP/ascomycin complex.
MeSH terms
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Binding Sites
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Calcineurin
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Calmodulin-Binding Proteins / antagonists & inhibitors
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Carbon Isotopes
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Carrier Proteins / chemistry*
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Carrier Proteins / metabolism
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Conformation
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Phosphoprotein Phosphatases / antagonists & inhibitors
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Protons
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Tacrolimus / analogs & derivatives*
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Tacrolimus / chemistry
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Tacrolimus Binding Proteins
Substances
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Calmodulin-Binding Proteins
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Carbon Isotopes
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Carrier Proteins
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Ligands
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Protons
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immunomycin
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Calcineurin
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Phosphoprotein Phosphatases
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Tacrolimus Binding Proteins
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Tacrolimus