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In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

Krücken J, Greif G, von Samson-Himmelstjerna G - Parasit Vectors (2009)

Bottom Line: In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa.In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, 30559 Hannover, Germany. juergen.kruecken@tiho-hannover.de.

ABSTRACT

Background: Cyclophilins (Cyps) are peptidyl cis/trans isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.

Results: BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of Cryptosporidium hominis, Toxoplasma gondii, Plasmodium falciparum, Theileria annulata, Theileria parva, and Babesia bovis. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7-9 for Cryptosporidia and 14 for T. gondii. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing.

Conclusion: The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.

No MeSH data available.


Mitochondrial Cyps. Domain architecture and genomic organization of mitochondrial Cyps. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); Mito, mitochondrial localization signal.
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Figure 4: Mitochondrial Cyps. Domain architecture and genomic organization of mitochondrial Cyps. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); Mito, mitochondrial localization signal.

Mentions: Putative Cyps with a mitochondrial localization signal at their NH2-terminus are schematically shown in Figure 4. The mitochondrial localization signal and a cleavage site were significantly predicted by MitoProt II [44] for TaCyp24.8 and TpCyp24.5. In contrast, cleavage site prediction was not possible for both PfCyp32.3 and BbCyp26.9. Nevertheless, MitoProt II predicts a high probability of mitochondrial localization and the algorithm PlasMit [45], which was specifically developed to predict mitochondrial proteins in Plasmodium, also suggest a mitochondrial localization of PfCyp32.3. Putative proteins of this Cyp subfamily could be detected only in the haemosporidia but neither in T. gondii nor in C. hominis. In T. gondii, mitochondrial PPIase activity might be achieved by the putative TgCyp31.8, a member of the subfamily of apicomplexa-specific Cyps (Figure 6). In contrast to all other members of this group, TgCyp31.8 is predicted to have an NH2-terminal mitochondrial localization signal. However, mitochondrial PPIase activity might also be dispensable in apicomplexan mitochondria as it is completely absent from the genomes of both C. hominis and C. muris.


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

Krücken J, Greif G, von Samson-Himmelstjerna G - Parasit Vectors (2009)

Mitochondrial Cyps. Domain architecture and genomic organization of mitochondrial Cyps. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); Mito, mitochondrial localization signal.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713222&req=5

Figure 4: Mitochondrial Cyps. Domain architecture and genomic organization of mitochondrial Cyps. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); Mito, mitochondrial localization signal.
Mentions: Putative Cyps with a mitochondrial localization signal at their NH2-terminus are schematically shown in Figure 4. The mitochondrial localization signal and a cleavage site were significantly predicted by MitoProt II [44] for TaCyp24.8 and TpCyp24.5. In contrast, cleavage site prediction was not possible for both PfCyp32.3 and BbCyp26.9. Nevertheless, MitoProt II predicts a high probability of mitochondrial localization and the algorithm PlasMit [45], which was specifically developed to predict mitochondrial proteins in Plasmodium, also suggest a mitochondrial localization of PfCyp32.3. Putative proteins of this Cyp subfamily could be detected only in the haemosporidia but neither in T. gondii nor in C. hominis. In T. gondii, mitochondrial PPIase activity might be achieved by the putative TgCyp31.8, a member of the subfamily of apicomplexa-specific Cyps (Figure 6). In contrast to all other members of this group, TgCyp31.8 is predicted to have an NH2-terminal mitochondrial localization signal. However, mitochondrial PPIase activity might also be dispensable in apicomplexan mitochondria as it is completely absent from the genomes of both C. hominis and C. muris.

Bottom Line: In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa.In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Parasitology, University of Veterinary Medicine Foundation, Bünteweg 17, 30559 Hannover, Germany. juergen.kruecken@tiho-hannover.de.

ABSTRACT

Background: Cyclophilins (Cyps) are peptidyl cis/trans isomerases implicated in diverse processes such as protein folding, signal transduction, and RNA processing. They are also candidate drug targets, in particular for the immunosuppressant cyclosporine A. In addition, cyclosporine is known to exhibit anti-parasitic effects on a wide range of organisms including several apicomplexa. In order to obtain new non-immunosuppressive drugs targeting apicomplexan cyclophilins, a profound knowledge of the cyclophilin repertoire of this phylum would be necessary.

Results: BLAST and maximum likelihood analyses identified 16 different cyclophilin subfamilies within the genomes of Cryptosporidium hominis, Toxoplasma gondii, Plasmodium falciparum, Theileria annulata, Theileria parva, and Babesia bovis. In addition to good statistical support from the phylogenetic analysis, these subfamilies are also confirmed by comparison of cyclophilin domain architecture. Within an individual genome, the number of different Cyp genes that could be deduced varies between 7-9 for Cryptosporidia and 14 for T. gondii. Many of the putative apicomplexan cyclophilins are predicted to be nuclear proteins, most of them presumably involved in RNA processing.

Conclusion: The genomes of apicomplexa harbor a cyclophilin repertoire that is at least as complex as that of most fungi. The identification of Cyp subfamilies that are specific for lower eukaryotes, apicomplexa, or even the genus Plasmodium is of particular interest since these subfamilies are not present in host cells and might therefore represent attractive drug targets.

No MeSH data available.