Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins

Abstract

The enzyme peptidyl-prolyl cis-trans isomerase (PPIase) was recently discovered in mammalian tissues and purified from porcine kidney. It catalyses the slow cis-trans isomerization of proline peptide (Xaa-Pro) bonds in oligopeptides and accelerates slow, rate-limiting steps in the folding of several proteins. Here, we report the N-terminal sequence of PPIase together with further chemical and enzymatic properties. The results indicate that this enzyme is probably identical to cyclophilin, a recently discovered mammalian protein which binds tightly to cyclosporin A (CsA). Cyclophilin is thought to be linked to the immunosuppressive action of CsA. The first 38 amino-acid residues of porcine PPIase and of bovine cyclophilin are identical and the two proteins both have a relative molecular mass of about 17,000 (ref. 7). The catalysis of prolyl isomerization in oligopeptides and of protein folding by PPIase are strongly inhibited in the presence of low levels of CsA. The activities of both PPIase and cyclophilin depend on a single sulphydryl group. At present it is unknown whether the inhibition of prolyl isomerase activity is related with the immunosuppressive action of CsA.

Inhibition of cyclophilin A suppresses H2O2‐enhanced replication of HCMV through the p38 MAPK signaling pathway

“…The CyPA activity was detected as previously described 24. The cis – trans isomerization of Ala‐Pro peptide bond in the test peptide N ‐succinyl‐Ala‐Ala‐Pro‐ p ‐nitroanilide (100 μ m ) was measured in an assay with α‐Chymotrypsin (10 μ m ).…”

Active site mutants of human cyclophilin A separate peptidyl‐prolyl isomerase activity from cyclosporin A binding and calcineurin inhibition

“…The encoded CyPs were expressed in E. coli and purified to homogeneity . Table 1 summarizes the catalytic efficiency, kcor/Km, of the mutant CyPs, assayed with N-succinyl-AAPF-pnitroanilide as the substrate (Fischer et al, 1989). These values were then normalized to the k,,/K,,, value of wild-type enzyme (16 pM-l SKI).…”

“…An 18-kDa protein, termed cyclophilin (CyP) due to its high affinity for cyclosporin A (CsA), has been proposed as the intracellular target (Handschumacher et al, 1984). CyP possesses enzymatic activity for cis-trans isomerization of peptidyl-prolyl bonds and may catalyze protein folding (Fischer et al, 1989;Takahashi et al, 1989;Schonbrunner et a]., 1991). CsA is a potent inhibitor (Kj = lop9 to M) of the PPIase activity of CyP (Kofron et al, 1991).…”

Extended binding sites of cyclophilin as revealed by the interaction with HIV‐1 Gag polyprotein derived oligopeptides

“…Cyclophilins, the cellular receptors for CsA [13], are known to possess peptidyl prolyl cis/trans isomerase (PPIase) activity [14]. This enzyme activity seems to improve the correct timing of those protein folding events in which a cis/trans Xaa-Pro isomer distribution transiently does not correspond to the thermodynamic equilibrium but reflects the immediate surrounding of the polypeptide chain.…”