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A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum.

Bhatt TK, Kapil C, Khan S, Jairajpuri MA, Sharma V, Santoni D, Silvestrini F, Pizzi E, Sharma A - BMC Genomics (2009)

Bottom Line: Using various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum.We have identified 37 Pf-aaRSs based on our bioinformatics analysis.Our data reveal several unique attributes in this protein family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. tkbhatt@icgeb.res.in

ABSTRACT

Background: Plasmodium parasites are causative agents of malaria which affects >500 million people and claims approximately 2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for protein translation and other vital cellular processes. We report an extensive analysis of the Plasmodium falciparum genome to identify and classify aaRSs in this organism.

Results: Using various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37 Pf-aaRS sequences contain signal peptides possibly directing them to different cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at various life cycle stages of the parasite; (iv) several PfaaRSs posses very unusual domain architectures; (v) phylogenetic analyses reveal evolutionary relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three dimensional structural modelling has provided insights which could be exploited in inhibitor discovery against parasite aaRSs.

Conclusion: We have identified 37 Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique attributes in this protein family. We have annotated all 37 Pf-aaRSs based on predicted localization, phylogenetics, domain architectures and their overall protein expression profiles. The sets of distinct features elaborated in this work will provide a platform for experimental dissection of this family of enzymes, possibly for the discovery of novel drugs against malaria.

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(a) Evolutionary tree was constructed using the PHYML based on maximum likelihood method. P. falciparum TyrRSs (PlasmoDB id -MAL8p1.125 and PF11_0181) are labeled as green triangles. One of the TryRSs (MAL8p1.125) is evolutionarily closer to H. sapiens whereas the other TyrRS (PF11_0181) is closer to E. coli. Total of 102 species were considered for the evolutionary analysis and were taken from three domains of life. (b) List of Pf-aaRS sequences evolutionarily closer to their E. coli and A. Thaliana counterparts.
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Figure 6: (a) Evolutionary tree was constructed using the PHYML based on maximum likelihood method. P. falciparum TyrRSs (PlasmoDB id -MAL8p1.125 and PF11_0181) are labeled as green triangles. One of the TryRSs (MAL8p1.125) is evolutionarily closer to H. sapiens whereas the other TyrRS (PF11_0181) is closer to E. coli. Total of 102 species were considered for the evolutionary analysis and were taken from three domains of life. (b) List of Pf-aaRS sequences evolutionarily closer to their E. coli and A. Thaliana counterparts.

Mentions: Overall the percentage identity between matching human and P. falciparum aaRS domains varies from 17 to 51. Clearly, Pf-aaRSs which have low sequence identity with human counterparts might serve as good drug targets. In order to study evolutionary relationships of P. falciparum aaRSs with other species, phylogenetic trees were developed in PHYML using maximum likelihood method. For each type of P. falciparum aaRS a separate tree was constructed (see additional file 2). aaRS sequences from 102 different species were used for multiple sequence alignments. As an example, phylogenetic tree of TyrRS from various species (including two sequences from P. falciparum) was constructed. Interestingly, one Pf-TyrRS (MAL8P1.125) clustered with human TyrRS whereas the second Pf-TyrRS (PF11_0181) clustered with bacterial TyrRS indicating different evolutionary origins (Figure 6a). Based on distance matrices, several P. falciparum aaRS sequences clustered as being closer to plants (A. thaliana) or to bacteria (E. coli) (Figure 6b). It is already known that apicomplexan parasites like P. falciparum house a secondary endosymbiotic plastid, possibly hijacked by lateral genetic transfer from an alga. Therefore, the P. falciparum aaRS sequences which are evolutionary close to bacteria and plants are likely to be the outcome of horizontal gene transfer from the plastid. P. falciparum contains ~12 such aaRS sequences which cluster with bacterial or plant sequences. Functional and structural characterization of these bacterial/plant-like aaRS may be relevant in focusing efforts at using aaRS as drug targets.


A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum.

Bhatt TK, Kapil C, Khan S, Jairajpuri MA, Sharma V, Santoni D, Silvestrini F, Pizzi E, Sharma A - BMC Genomics (2009)

(a) Evolutionary tree was constructed using the PHYML based on maximum likelihood method. P. falciparum TyrRSs (PlasmoDB id -MAL8p1.125 and PF11_0181) are labeled as green triangles. One of the TryRSs (MAL8p1.125) is evolutionarily closer to H. sapiens whereas the other TyrRS (PF11_0181) is closer to E. coli. Total of 102 species were considered for the evolutionary analysis and were taken from three domains of life. (b) List of Pf-aaRS sequences evolutionarily closer to their E. coli and A. Thaliana counterparts.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2813244&req=5

Figure 6: (a) Evolutionary tree was constructed using the PHYML based on maximum likelihood method. P. falciparum TyrRSs (PlasmoDB id -MAL8p1.125 and PF11_0181) are labeled as green triangles. One of the TryRSs (MAL8p1.125) is evolutionarily closer to H. sapiens whereas the other TyrRS (PF11_0181) is closer to E. coli. Total of 102 species were considered for the evolutionary analysis and were taken from three domains of life. (b) List of Pf-aaRS sequences evolutionarily closer to their E. coli and A. Thaliana counterparts.
Mentions: Overall the percentage identity between matching human and P. falciparum aaRS domains varies from 17 to 51. Clearly, Pf-aaRSs which have low sequence identity with human counterparts might serve as good drug targets. In order to study evolutionary relationships of P. falciparum aaRSs with other species, phylogenetic trees were developed in PHYML using maximum likelihood method. For each type of P. falciparum aaRS a separate tree was constructed (see additional file 2). aaRS sequences from 102 different species were used for multiple sequence alignments. As an example, phylogenetic tree of TyrRS from various species (including two sequences from P. falciparum) was constructed. Interestingly, one Pf-TyrRS (MAL8P1.125) clustered with human TyrRS whereas the second Pf-TyrRS (PF11_0181) clustered with bacterial TyrRS indicating different evolutionary origins (Figure 6a). Based on distance matrices, several P. falciparum aaRS sequences clustered as being closer to plants (A. thaliana) or to bacteria (E. coli) (Figure 6b). It is already known that apicomplexan parasites like P. falciparum house a secondary endosymbiotic plastid, possibly hijacked by lateral genetic transfer from an alga. Therefore, the P. falciparum aaRS sequences which are evolutionary close to bacteria and plants are likely to be the outcome of horizontal gene transfer from the plastid. P. falciparum contains ~12 such aaRS sequences which cluster with bacterial or plant sequences. Functional and structural characterization of these bacterial/plant-like aaRS may be relevant in focusing efforts at using aaRS as drug targets.

Bottom Line: Using various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum.We have identified 37 Pf-aaRSs based on our bioinformatics analysis.Our data reveal several unique attributes in this protein family.

View Article: PubMed Central - HTML - PubMed

Affiliation: Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. tkbhatt@icgeb.res.in

ABSTRACT

Background: Plasmodium parasites are causative agents of malaria which affects >500 million people and claims approximately 2 million lives annually. The completion of Plasmodium genome sequencing and availability of PlasmoDB database has provided a platform for systematic study of parasite genome. Aminoacyl-tRNA synthetases (aaRSs) are pivotal enzymes for protein translation and other vital cellular processes. We report an extensive analysis of the Plasmodium falciparum genome to identify and classify aaRSs in this organism.

Results: Using various computational and bioinformatics tools, we have identified 37 aaRSs in P. falciparum. Our key observations are: (i) fraction of proteome dedicated to aaRSs in P. falciparum is very high compared to many other organisms; (ii) 23 out of 37 Pf-aaRS sequences contain signal peptides possibly directing them to different cellular organelles; (iii) expression profiles of Pf-aaRSs vary considerably at various life cycle stages of the parasite; (iv) several PfaaRSs posses very unusual domain architectures; (v) phylogenetic analyses reveal evolutionary relatedness of several parasite aaRSs to bacterial and plants aaRSs; (vi) three dimensional structural modelling has provided insights which could be exploited in inhibitor discovery against parasite aaRSs.

Conclusion: We have identified 37 Pf-aaRSs based on our bioinformatics analysis. Our data reveal several unique attributes in this protein family. We have annotated all 37 Pf-aaRSs based on predicted localization, phylogenetics, domain architectures and their overall protein expression profiles. The sets of distinct features elaborated in this work will provide a platform for experimental dissection of this family of enzymes, possibly for the discovery of novel drugs against malaria.

Show MeSH
Related in: MedlinePlus