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


CONCLUSIONS
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.
Bhatt
Tarun Kumar
TK
Structural and Computational Biology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India. tkbhatt@icgeb.res.in
Kapil
Charu
C
Khan
Sameena
S
Jairajpuri
Mohamad Aman
MA
Sharma
Vinay
V
Santoni
Daniele
D
Silvestrini
Francesco
F
Pizzi
Elisabetta
E
Sharma
Amit
A
D000595:Amino Acid Sequence; D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D019295:Computational Biology; D018503:Genome, Protozoan / Q000235:genetics*; D016778:Malaria, Falciparum / Q000469:parasitology*; D008969:Molecular Sequence Data; D010802:Phylogeny; D010963:Plasmodium falciparum / Q000201:enzymology* / Q000235:genetics* / Q000502:physiology; D017433:Protein Structure, Secondary; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D015800:Protozoan Proteins; D000604:Amino Acyl-tRNA Synthetases