Disease relevance of PPIA

• Although cyclosporin A (CsA), an inhibitory ligand of cyclophilin A, is a widely used immunosuppressive drug, it causes arterial hypertension in part by impairing eNOS-dependent vasodilation [1].
• Cyclophilin A from the bovine parasite Trypanosoma brucei brucei has been cloned, expressed in Escherichia coli, purified and crystallized in the presence of cyclosporin A using ammonium sulfate as a precipitant [2].

High impact information on PPIA

• The Ca(2+)- and calmodulin-dependent protein phosphatase calcineurin is inhibited by the immunosuppressant drug cyclosporin A in the presence of cyclophilin A or B [3].
• Cyclophilin, a specific cyclosporin A-binding protein has been purified to homogeneity from human spleen and bovine thymus cytosol [4].
• IC50 values for calf-thymus CypA were obtained by kinetic evaluation of its cis-->trans isomerase activity [5].
• Further work is needed in order to delineate the role of CypA in the cell cycle and its relation to the action of CsA [6].
• In mitotic cells CypA is increased in amount and redistributed away from cytoplasmic organelles [6].

Anatomical context of PPIA

• High levels of CypA were demonstrated in murine splenic erythroblasts and myeloblasts, but they became undetectable during differentiation to mature erythrocytes and granulocytes [6].

Associations of PPIA with chemical compounds

• We raised rabbit antisera against homogeneous bovine cyclophilin A (CypA) and we report their use for its immunofluorescent and immunochemical detection without resorting to cyclosporine binding [6].
• Cyclophilin A, a peptidyl-prolyl cis-trans is isomerase that catalyzes the otherwise slow isomerization of Xaa-Pro imidic bond, specifically binds the immunosuppressant cyclosporin A [7].

Other interactions of PPIA

• Cyclophilin-B is an abundant protein whose conformation is similar to cyclophilin-A [8].
• The Pro1 residue of cyclolinopeptide A seems to play a fundamental role in determining the inhibition of the rotamase activity of cyclophilin A, as the homodetic analogue lacking this residue does not show any inhibitory ability [9].

Analytical, diagnostic and therapeutic context of PPIA

• Dot blot immunoassays demonstrated that murine tissues contain similar amounts of CypA [6].
• Indirect immunofluorescence demonstrated that in tissue culture cells CypA is present in the cytoplasm diffusely and also associated with vesicles and the Golgi apparatus [6].
• The psiPro-containing CsC derivatives exhibit enhanced conformational backbone rigidity, as suggested by analytical HPLC, NMR spectroscopy and by kinetic measurements on binding with their receptor protein cyclophilin A (CypA) that were not time-dependent [5].
• Circular dichroism spectroscopy revealed that bovine cyclophilin-A (bCyP-18) and bCyP-20 in aqueous solution have similar conformations [8].
• Expression, purification, crystallization and preliminary X-ray analysis of cyclophilin A from the bovine parasite Trypanosoma brucei brucei [2].

References