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FKBPFK506 Binding Protein
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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.
Fotuhi et al., "High brain densities of the immunophilin FKBP colocalized with calcineurin," Nature, vol.
Konsolaki, "FKBP immunophilins and Alzheimer's disease: a chaperoned affair," Journal of Biosciences, vol.
FKBP52 couldbindwithsteroid receptors in FKBPs [19].
Furthermore, FKBP52 will have a higher binding affinity for HSP90 and steroid receptors (which could act as a cochaperone [28,29]) than FKBP51, which has a similar structure to FKBPs and can make microtubules more stable [20, 30].
[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)