Limits...
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.


Cyps with WD40 repeats. Domain architecture and genomic organization of Cyps with WD40 repeats. Species are abbreviated as in Fig. 1. NLS, nuclear localization signal; WD40 repeat (CD accession-no.: [cl02567]), Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); NR, Asp-rich region; KR, Lys-rich region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2713222&req=5

Figure 10: Cyps with WD40 repeats. Domain architecture and genomic organization of Cyps with WD40 repeats. Species are abbreviated as in Fig. 1. NLS, nuclear localization signal; WD40 repeat (CD accession-no.: [cl02567]), Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); NR, Asp-rich region; KR, Lys-rich region.

Mentions: The first group of putative Cyps with a non-Cyp_ABH domain is represented by the WD40 repeat-containing Cyps which are encoded in all apicomplexan genomes analyzed here (Figure 1). This subfamily contains multi-domain Cyps with a Cyp_WD40 domain (CD accession-no: [cd01927]) in its COOH-terminus (Figure 10). WD40 domains (CD accession no.: [cl02567]) are characterized by repeats of about 40 amino acids containing a characteristic Trp/Asp dipeptide. The length of the deduced WD40 domain ranges from 145 amino acids in P. falciparum to 321 and 328 amino acids in C. hominis and T. gondii, respectively. The WD40 repeat domain is either located close to the NH2-terminus as in Theileria species and in B. bovis, or is preceded by a longer NH2-terminal extension without identifiable domains or motifs as in T. gondii, P. falciparum, and C. hominis. There is no sequence similarity between the orthologs within this region. In T. gondii, however, a nuclear localization signal can be found here, and in P. falciparum there are two short stretches rich in Asn and Lys, respectively. An orthologous protein from E. tenella has recently been described to contain a very Ser- and His-rich NH2-terminus [29].


In silico analysis of the cyclophilin repertoire of apicomplexan parasites.

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

Cyps with WD40 repeats. Domain architecture and genomic organization of Cyps with WD40 repeats. Species are abbreviated as in Fig. 1. NLS, nuclear localization signal; WD40 repeat (CD accession-no.: [cl02567]), Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); NR, Asp-rich region; KR, Lys-rich region.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 10: Cyps with WD40 repeats. Domain architecture and genomic organization of Cyps with WD40 repeats. Species are abbreviated as in Fig. 1. NLS, nuclear localization signal; WD40 repeat (CD accession-no.: [cl02567]), Cyp_ABH, ABH-type Cyp domain (CD accession-no.: [cd01926]); NR, Asp-rich region; KR, Lys-rich region.
Mentions: The first group of putative Cyps with a non-Cyp_ABH domain is represented by the WD40 repeat-containing Cyps which are encoded in all apicomplexan genomes analyzed here (Figure 1). This subfamily contains multi-domain Cyps with a Cyp_WD40 domain (CD accession-no: [cd01927]) in its COOH-terminus (Figure 10). WD40 domains (CD accession no.: [cl02567]) are characterized by repeats of about 40 amino acids containing a characteristic Trp/Asp dipeptide. The length of the deduced WD40 domain ranges from 145 amino acids in P. falciparum to 321 and 328 amino acids in C. hominis and T. gondii, respectively. The WD40 repeat domain is either located close to the NH2-terminus as in Theileria species and in B. bovis, or is preceded by a longer NH2-terminal extension without identifiable domains or motifs as in T. gondii, P. falciparum, and C. hominis. There is no sequence similarity between the orthologs within this region. In T. gondii, however, a nuclear localization signal can be found here, and in P. falciparum there are two short stretches rich in Asn and Lys, respectively. An orthologous protein from E. tenella has recently been described to contain a very Ser- and His-rich NH2-terminus [29].

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.