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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.


PPIL3-like Cyps. Domain architecture and genomic organization of PPIL3-like Cyps. Species are abbreviated as in Fig. 1. Cyp_PPIL3, PPIL3-type Cyp domain (CD accession-no: [cd01928]).
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Figure 11: PPIL3-like Cyps. Domain architecture and genomic organization of PPIL3-like Cyps. Species are abbreviated as in Fig. 1. Cyp_PPIL3, PPIL3-type Cyp domain (CD accession-no: [cd01928]).

Mentions: Within the non Cyp_ABH group, the PPIL3-like Cyps are the only subfamily of small single domain Cyps that is widely distributed among apicomplexa. PPIL3-like Cyps can be predicted in all the apicomplexan genomes and consist of little more than the Cyp_PPIL3 domain (accession-no.: [cd01928]) itself (Figures 1 and 11). Since apparent localization signals are missing, a predominant cytosolic localization of the putative proteins might be assumed. However, at least one splice form of human PPIL3 has been identified as part of the B complex of the spliceosome in the nucleus [38] though its precise role in the spliceosome B complex has not been analyzed yet.


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

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

PPIL3-like Cyps. Domain architecture and genomic organization of PPIL3-like Cyps. Species are abbreviated as in Fig. 1. Cyp_PPIL3, PPIL3-type Cyp domain (CD accession-no: [cd01928]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 11: PPIL3-like Cyps. Domain architecture and genomic organization of PPIL3-like Cyps. Species are abbreviated as in Fig. 1. Cyp_PPIL3, PPIL3-type Cyp domain (CD accession-no: [cd01928]).
Mentions: Within the non Cyp_ABH group, the PPIL3-like Cyps are the only subfamily of small single domain Cyps that is widely distributed among apicomplexa. PPIL3-like Cyps can be predicted in all the apicomplexan genomes and consist of little more than the Cyp_PPIL3 domain (accession-no.: [cd01928]) itself (Figures 1 and 11). Since apparent localization signals are missing, a predominant cytosolic localization of the putative proteins might be assumed. However, at least one splice form of human PPIL3 has been identified as part of the B complex of the spliceosome in the nucleus [38] though its precise role in the spliceosome B complex has not been analyzed yet.

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.