Abstract
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.
Publication types
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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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Animals
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Antifungal Agents / isolation & purification
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Antifungal Agents / pharmacology*
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Brain
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Carrier Proteins / chemistry*
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Carrier Proteins / isolation & purification
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Carrier Proteins / pharmacology
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Cattle
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Circular Dichroism
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Cyclohexanols / chemistry*
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Cyclohexanols / pharmacology
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Databases, Factual
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Immunosuppressive Agents / isolation & purification
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Immunosuppressive Agents / pharmacology*
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Molecular Sequence Data
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Molecular Weight
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Peptides / chemistry
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Peptides / isolation & purification
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Polyenes / isolation & purification
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Polyenes / pharmacology*
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Protein Conformation
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Pyrans / chemistry*
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Pyrans / pharmacology
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Sequence Alignment
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Sirolimus
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Spleen
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Tacrolimus / pharmacology
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Thymus Gland
Substances
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Antifungal Agents
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Carrier Proteins
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Cyclohexanols
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Immunosuppressive Agents
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Peptides
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Polyenes
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Pyrans
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immunophilin ligand 506BD
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Sirolimus
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Tacrolimus
Associated data
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GENBANK/M84588
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GENBANK/M84589
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GENBANK/M84590
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GENBANK/M84591
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GENBANK/M84592
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GENBANK/M84593
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GENBANK/M84594
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GENBANK/M84595
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GENBANK/M84596
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GENBANK/M95123
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PIR/A40050