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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.


FCBP proteins. Domain architecture and genomic organization of FCBPs from apicomplexa. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); FKBP, FK506-binding domain (PFAM accession-no.: [pfam00254]); TPR, Tetratricopeptide repeat (InterProScan accession-no.: [IPR001440]).
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Figure 8: FCBP proteins. Domain architecture and genomic organization of FCBPs from apicomplexa. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); FKBP, FK506-binding domain (PFAM accession-no.: [pfam00254]); TPR, Tetratricopeptide repeat (InterProScan accession-no.: [IPR001440]).

Mentions: The next multi-domain Cyp subfamily to be described here are the recently identified FCBP proteins [28] which contain two phylogenetically unrelated PPIase domains, i.e. an FK506-binding domain (FKBP) at the NH2-terminus and a Cyp_ABH type domain in the COOH-terminus (Figure 8). Between these two enzymatic domains, there are three tetratricopeptide repeat domains (TRP) [cd00189] which are typically involved in protein/protein interactions and might contribute to recruitment of specific substrates for FCBP proteins.


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

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

FCBP proteins. Domain architecture and genomic organization of FCBPs from apicomplexa. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); FKBP, FK506-binding domain (PFAM accession-no.: [pfam00254]); TPR, Tetratricopeptide repeat (InterProScan accession-no.: [IPR001440]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: FCBP proteins. Domain architecture and genomic organization of FCBPs from apicomplexa. Species are abbreviated as in Fig. 1. Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); FKBP, FK506-binding domain (PFAM accession-no.: [pfam00254]); TPR, Tetratricopeptide repeat (InterProScan accession-no.: [IPR001440]).
Mentions: The next multi-domain Cyp subfamily to be described here are the recently identified FCBP proteins [28] which contain two phylogenetically unrelated PPIase domains, i.e. an FK506-binding domain (FKBP) at the NH2-terminus and a Cyp_ABH type domain in the COOH-terminus (Figure 8). Between these two enzymatic domains, there are three tetratricopeptide repeat domains (TRP) [cd00189] which are typically involved in protein/protein interactions and might contribute to recruitment of specific substrates for FCBP proteins.

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.