FKBP [1,2,3] is the major high-affinity binding protein, in vertebrates, for
the immunosuppressive drug FK506. It exhibits peptidyl-prolyl cis-trans
isomerase activity (EC 5.2.1.8) (PPIase or rotamase). PPIase is an enzyme that
accelerates protein folding by catalyzing the cis-trans isomerization of
proline imidic peptide bonds in oligopeptides [4].
At least three different forms of FKBP are known in mammalian species:
FKBP-12, which is cytosolic and inhibited by both FK506 and rapamycin.
FKBP-13, which is membrane associated and inhibited by both FK506 and
rapamycin.
FKBP-25, which is preferentially inhibited by rapamycin.
These forms of FKBP are evolutionary related and show extensive similarities
[5,6,7] with the following proteins:
Fungal FKBP.
Mammalian hsp binding immunophilin (HBI) (also called p59). HBI is a
protein which binds to hsp90 and contains two FKBP-like domains in its N-
terminal section - the first of which seems to be functional.
The C-terminal part of the cell-surface protein mip from Legionella;
a protein associated with macrophage infection by an unknown mechanism.
Escherichia coli slyD [8], a protein with a N-terminal FKBP domain followed
by an histidine-rich metal-binding domain.
Escherichia coli fkpA.
Escherichia coli fklB (FKBP22).
Escherichia coli slpA.
Bacterial trigger factor (Tig).
Streptomyces hygroscopus and chrysomallus FK506-binding protein.
Chlamydia trachomatis 27 Kd membrane protein.
Neisseria meningitidis strain C114 PPiase.
Probable PPiases from Haemophilus influenzae (HI0754), Methanococcus
jannaschii (MJ0278 and MJ0825), Pseudomonas fluorescens and Pseudomonase
aeruginosa.
We developed a profile for FKBP that spans the complete domain.
Note:
Cyclophilin, the protein that binds to the immunosuppressive drug
cyclosporin A, is also a PPIase but its sequence is not at all related to
that of FKBP (see <PDOC00154>).
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