Stereospecific assignments and chi 1 rotamers for FKBP when bound to ascomycin from 3JH alpha,H beta and 3HN,H beta coupling constants.
3JH alpha,H beta and 3JN,H beta coupling constants were measured for isotopically labeled FKBP when bound to the immunosuppressant, ascomycin, using a 1H-coupled 3D HCCH-TOCSY and 15N-coupled 3D HSQC-TOCSY experiment, respectively. From an analysis of these two sets of coupling constants, stereospecific beta-proton assignments and chi 1 rotamers for FKBP have been obtained. All of the chi 1 rotamers were consistent with the chi 1 angles measured in the X-ray crystal structure of the FKBP/FK506 complex, suggesting that the structures of the two complexes are similar.
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Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064.
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D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D011522:Protons; D011994:Recombinant Proteins / Q000378:metabolism; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins; D014961:X-Ray Diffraction
D002352:Carrier Proteins; D011522:Protons; D011994:Recombinant Proteins; C058028:immunomycin; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus