Identification and characterization of novel Plasmodium falciparum cyclophilins and their roles in the antimalarial actions of cyclosporin A and derivatives

Background Cyclophilins are distributed widely among different organisms and are proposed drug targets for a number of diseases including HIV and hepatitis C infection and ischemia. Cyclophilins play roles in folding and chaperoning of cellular proteins and are the major receptors for the immunosupp...

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Bibliographic Details
Published in:Malaria journal 2010-10, Vol.9 (S2), p.1-3, Article O3
Main Authors: Marin-Menendez, Alejandro, Bell, Angus
Format: Article
Language:English
Subjects:
Antimalarial activity
Antimalarial agents
Bibliometrics
Colour
Cyclosporin A
Drugs
E coli
Erythrocytes
Genes
Genomes
Hepatitis
Hepatitis C
HIV
Human immunodeficiency virus
Identification
Immunosuppressive agents
Informetrics
Ischemia
Malaria
Medical research
Mitochondria
Nickel
Nucleic acids
Open access
Oral Presentation
Parasites
Peptidylprolyl isomerase
Plasmodium falciparum
Proteins
Receptors
Ribonucleic acid
RNA
Splicing factors
Therapeutic targets
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Summary:Background Cyclophilins are distributed widely among different organisms and are proposed drug targets for a number of diseases including HIV and hepatitis C infection and ischemia. Cyclophilins play roles in folding and chaperoning of cellular proteins and are the major receptors for the immunosuppressive drug cyclosporin A (CsA). CsA and certain non-immunosuppressive derivatives (e.g., valspodar) possess potent antimalarial activity. We are interested in the role (if any) played by cyclophilins in parasite killing by cyclosporins. We, and others, have previously characterized two CsA-binding cyclophilins (PfCYP19A and PfCYP19B) but a family of genes encoding uncharacterized cyclophilins/cyclophilin-like proteins is also seen in the P. falciparum genome (Figure 1). Figure 1 figure1 Domain architectures of P. falciparum cyclophilin and cyclophilin-like proteins annotated in PlasmoDB. Differently-coloured boxes indicate recognizable domains; red boxes indicate cyclophilin/cyclophilin-like domains with numbers indicating % identities to human cyclophilin A(hCYP18). RRM, RNA recognition motif; SP, signal peptide; putMito, putative mitochondrial signal; SYF2, splicing factor 2; WD40, WD40 domain. Full size image
ISSN:1475-2875
1475-2875
DOI:10.1186/1475-2875-9-S2-O3