FKBP

FKBP

FKBP, or FK506 binding protein, is a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence.Siekierka, J.J., Hung, S.H., Poe, M., Lin, C.S.and Sigal, N.H. A cytosolic binding protein for the immunosuppressant FK-506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin. (1989) Nature. 341:755. PMID 2477714] FKBPs have been identified in many eukaryotes from yeast to humans and function as protein folding chaperones for proteins containing proline residues. Along with cyclophilin, FKBPs belong to the immunophilin family.Balbach J, Schmid FX. (2000). Proline isomerization and its catalysis in protein folding. "In Mechanisms of Protein Folding" 2nd ed. Ed. RH Pain. "Frontiers in Molecular Biology" series. Oxford University Press: Oxford, UK.]

FKBP12 is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients suffering from autoimmune disorders. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin. Mayer DA et al. (1997). MULTICENTER RANDOMIZED TRIAL COMPARING TACROLIMUS (FK506) AND CYCLOSPORINE IN THE PREVENTION OF RENAL ALLOGRAFT REJECTION 1: A Report of the European Tacrolimus Multicenter Renal Study Group. "Transplantation". 64(3):436-443. PMID 9275110] Both the FKBP-tacrolimus complex and the ciclosporin-cyclophilin complex inhibit a phosphatase called calcineurin, thus blocking signal transduction in the T-lymphocyte transduction pathway.Liu J, Farmer J, Lane W, Friedman J, Weissman I, Schreiber S. (1991). Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. "Cell" 66 (4): 807-15. PMID 1715244] This therapeutic role is not related to prolyl isomerase activity.

References

External links

* [http://www.lhsc.on.ca/transplant/drugs.htm Anti-rejection drugs]


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