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Gene Review:

PFL0735w - cyclophilin

Plasmodium falciparum 3D7

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Disease relevance of PFL0735w

We have cloned and overexpressed in Escherichia coli a gene encoding a CyP from Plasmodium falciparum (PfCyP19) that is located on chromosome 3 [1].
Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii [2].

High impact information on PFL0735w

The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A [3].
The two analogs that were most active in inhibiting C. parvum, SDZ PSC-833 and SDZ 033-243, bind weakly to cyclophilin, a peptidyl proline isomerase which is the primary target of cyclosporine and CS analogs [4].
Here we report that cyclosporin A (CsA), an inhibitor of parasitic cyclophilin (Cyp) and protein phosphatase 2B (calcineurin, CN), acted synergistically with GA to inhibit the erythrocytic growth of the parasite [5].
A possible explanation is that the antimalarial effect of CLA and analogues may result from their influence on cell membranes rather than on some specific receptor such as cyclophilin [6].

References

Detailed characterization of a cyclophilin from the human malaria parasite Plasmodium falciparum. Berriman, M., Fairlamb, A.H. Biochem. J. (1998) [Pubmed]
Inhibition of HIV-1 infection by a CCR5-binding cyclophilin from Toxoplasma gondii. Golding, H., Aliberti, J., King, L.R., Manischewitz, J., Andersen, J., Valenzuela, J., Landau, N.R., Sher, A. Blood (2003) [Pubmed]
The three-dimensional structure of a Plasmodium falciparum cyclophilin in complex with the potent anti-malarial cyclosporin A. Peterson, M.R., Hall, D.R., Berriman, M., Nunes, J.A., Leonard, G.A., Fairlamb, A.H., Hunter, W.N. J. Mol. Biol. (2000) [Pubmed]
Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum. Perkins, M.E., Wu, T.W., Le Blancq, S.M. Antimicrob. Agents Chemother. (1998) [Pubmed]
Plasmodium falciparum calcineurin and its association with heat shock protein 90: mechanisms for the antimalarial activity of cyclosporin A and synergism with geldanamycin. Kumar, R., Musiyenko, A., Barik, S. Mol. Biochem. Parasitol. (2005) [Pubmed]
Antimalarial activity of cyclolinopeptide A and its analogues. Bell, A., McSteen, P.M., Cebrat, M., Picur, B., Siemion, I.Z. Acta poloniae pharmaceutica. (2000) [Pubmed]

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