A rapamycin-selective 25-kDa immunophilin.
FKBP25, a previously uncharacterized 25-kDa FK506- and rapamycin-binding protein, was purified to homogeneity from calf thymus, brain, and spleen, and the sequence of a 215 amino acid (aa) 24-kDa C-terminal peptide was established. The N-terminal domain (101 aa) is unrelated to any known protein, is hydrophilic, and is predicted by circular dichroism spectroscopy to be largely alpha-helix. The C-terminal domain (114 aa) is homologous to FKBP12 and other FKBPs but has a potential nuclear targeting sequence and a unique insertion of seven amino acids in one of its loops. FKBP25 displays the rotamase activity characteristic of FKBPs; the activity is inhibited by the immunosuppressants rapamycin (Ki = 0.9 nM) and FK506 (Ki = 160 nM), but not cyclosporin A. The protein, its rapamycin selectivity, and the potential nuclear targeting sequence are discussed in terms of the structure of hFKBP12.
Galat
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A
Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
Lane
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WS
Standaert
R F
RF
Schreiber
S L
SL
D000595:Amino Acid Sequence; D000818:Animals; D000935:Antifungal Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001921:Brain; D002352:Carrier Proteins / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D002417:Cattle; D002942:Circular Dichroism; D003511:Cyclohexanols / Q000737:chemistry* / Q000494:pharmacology; D016208:Databases, Factual; D007166:Immunosuppressive Agents / Q000302:isolation & purification / Q000494:pharmacology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification; D011090:Polyenes / Q000302:isolation & purification / Q000494:pharmacology*; D011487:Protein Conformation; D011714:Pyrans / Q000737:chemistry* / Q000494:pharmacology; D016415:Sequence Alignment; D020123:Sirolimus; D013154:Spleen; D016559:Tacrolimus / Q000494:pharmacology; D013950:Thymus Gland
D000935:Antifungal Agents; D002352:Carrier Proteins; D003511:Cyclohexanols; D007166:Immunosuppressive Agents; D010455:Peptides; D011090:Polyenes; D011714:Pyrans; C066205:immunophilin ligand 506BD; D020123:Sirolimus; D016559:Tacrolimus