As a unique member of the FKBP family, FKBP38 contains three types of domains: FKBP-type peptidyl-prolyl cis-trans isomerase (FKBP_C), tetratricopeptide repeat domain (TPR).
These features are similar to those of Rheb and FKBP38 in other species, indicating that the deduced goat Rheb protein has Ras-like small GTPase activity and that FKBP38 has intrinsic FKBP family activity.
[4] Nonstandard abbreviations: CNI, calcineurin inhibitor; MMF, mycophenolate mofetil; CNA, calcineurin activity; PD, pharmacodynamic; CsA, cyclosporin A; TRL, tacrolimus; IL, interleukin; IFN, interferon; FKBP, FK-binding protein; PK, pharmacokinetic; AUC, area under the curve; NHC, healthy control; DTT, dithiothreitol; PHA, phytohemagglutinin; TFA, trifluoroacetic acid; AP, alkaline phosphatase; PBMC, peripheral blood mononuclear cell; and MPA, mycophenolic acid.
To inhibit CNA, CsA and TRL must bind to the immunophilins present in the cytoplasm of T lymphocytes: cyclophilins in the case of CsA and FK-binding proteins (FKBPs) in the case of TRL.
Structure-function relationships in the FK506-binding protein (FKBP) family of peptidylprolyl cis-trans isomerases.
(3) Nonstandard abbreviations: PPIase, peptidylprolyl cis/trans isomerase, Cyp, cyclophilin; FKBP, FK506 binding protein; GGT, [gamma]-glutamyltransferase; AP, alkaline phosphatase; and LDH, lactate dehydrogenase.
Rapamycin binds to the same intracellular binding protein in lymphocytes (
FKBP or FK-506 binding protein) as its structural homolog, the immunosuppressive drug FK-506 [3], and inhibits the S6p70-kinase [4], an immunosuppressive mechanism of drug biological action quite different from that of FK-506 (tacrolimus), which inhibits the phosphatase activity of calcineurin in vitro [5].(3)