Exon organization of the human FKBP-12 gene: Correlation with structural and functional protein domains

Journal Article · Tue Sep 03 00:00:00 EDT 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00099a002· OSTI ID:5822260

DiLella, A G; Craig, R J ^[1]

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1. SmithKline Beecham Pharmaceuticals, King of Prussia, PA (United States)

FKBP-12, the major T-cell binding protein for the immunosuppressive agents FK506 and rapamycin, catalyzes the interconversion of the cis and trans rotamers of the peptidyl-prolyl amide bond of peptide and protein substrates. The function of rotamase activity in cells and the role of FKBP-12 in immunoregulation is uncertain. In this paper the authors report the cloning and characterization of the human chromosomal FKBP-12 gene and four processed FKBP-12 pseudogenes. The FKBP-12 gene is 24 kilobases in length and contains five exons. The protein-coding region of the gene is divided into four exon modules that correlate with the structural and functional domains of the protein. The novel structure of FKBP-12 resulting form the topology of the antiparallel {beta}-sheet is the topological crossing of two loops that are encoded by separate exons. Separate exons also encode the antiparallel {beta}-sheet and {alpha}-helical region that define the drug-binding pocket and enzyme activity site of FKBP-12. The exon organization of the FKBP-12 gene structure will enable inactivation of this gene by homologous recombination in cells to provide a model to study the role of FKBP-12 in immunoregulation and normal cellular processes.

• OSTI ID: 5822260
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:35; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AMINO ACID SEQUENCE
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CHEMICAL ACTIVATION
CONNECTIVE TISSUE CELLS
DNA SEQUENCING
DRUGS
GENES
IMMUNOSUPPRESSIVE DRUGS
ISOMER SHIFT
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MAN
MATERIALS
MEMBRANE PROTEINS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
PRIMATES
PROTEINS
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
VERTEBRATES