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. 2014 Aug 26:5:291.
doi: 10.3389/fgene.2014.00291. eCollection 2014.

Insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in Leishmania donovani

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Insilico analysis of hypothetical proteins unveils putative metabolic pathways and essential genes in Leishmania donovani

Nithin Ravooru et al. Front Genet. .

Abstract

Leishmaniasis is a parasitic disease caused by the protozoan Leishmania, which is active in two broad forms namely, Visceral Leishmaniasis (VL or Kala Azar) and Cutaneous Leishmaniasis (CL). The disease is most prevalent in the tropical regions and poses a threat to over 70 countries across the globe. About 200 million people are estimated to be at risk of developing VL in the Indian subcontinent, and this refers to around 67% of the global VL disease burden. The Indian state of Bihar alone accounts for 50% of the total VL cases. While no vaccination exists, several pentavalent antimonials and drugs like Paromomycin, Amphotericin, Miltefosine etc. are used in the treatment of Leishmaniasis. However, due to their low efficacies and the resistance developed by the bug to these medications, there is an urgent need to look into newer species specific targets. The proteome information available suggests that among the 7960 proteins in Leishmania donavani, a staggering 65% remains classified as a hypothetical uncharacterized set. In this background, we have attempted to assign probable functions to these hypothetical sequences present in this parasite, to explore their plausible roles as druggable receptors. Thus, putative functions have been defined to 105 hypothetical proteins, which exhibited a GO term correlation and PFAM domain coverage of more than 50% over the query sequence length. Of these, 27 sequences were found to be associated with a reference pathway in KEGG as well. Further, using homology approaches, four pathways viz., Ubiquinone biosynthesis, Fatty acid elongation in Mitochondria, Fatty Acid Elongation in ER and Seleno-cysteine Metabolism have been reconstructed. In addition, 7 new putative essential genes have been mined with the help of Eukaryotic Database of Essential Genes (DEG). All these information related to pathways and essential genes indeed show promise for exploiting the select molecules as potential therapeutic targets.

Keywords: Leishmania donovani; drug targets; fatty acid elongation; hypothetical proteins; seleno-cysteine metabolism; ubiquinone biosynthesis.

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Figures

Figure 1
Figure 1
Protocol used in sequence processing.
Figure 2
Figure 2
(A) Distribution of biological process of the 105 sequences. (B) Distribution of molecular function of the 105 sequences. (C) Distribution of cellular component of the 105 sequences.
Figure 3
Figure 3
Protocol depicting steps in homology based pathway reconstruction.
Figure 4
Figure 4
(A) COG network for members of Ubiquinone biosynthesis Pathway. (B) Phylogenetic profile of the members of Ubiquinone biosynthesis Pathway.
Figure 5
Figure 5
(A) COG network display for members of Fatty Acid Elongation (Mitochondria) Pathway. (B) Phylogenetic profile of the members of Fatty Acid Elongation (Mitochondria) Pathway.
Figure 6
Figure 6
(A) COG network display for members of Fatty Acid Elongation (in ER) Pathway. (B) Phylogenetic profile of the members of Fatty Acid Elongation (in ER) Pathway.
Figure 7
Figure 7
(A) COG network display for members of Seleno-cysteine metabolism Pathway. (B) Phylogenetic profile of the members of Seleno-cysteine metabolism Pathway.
Figure 8
Figure 8
Phylogenetic tree comprising 12 query associated to 32 DEG hits (The taxa colored in Red correspond to sequences belonging to WD40 superfamily while E9BCZ9, colored in blue is closely related to Nep1, a methyltranferase involved in ribosomal biogenesis).
Figure 9
Figure 9
(A) COG network of the hypothetical protein (E9BCZ9) and its interacting members. (B) Phylogenetic co-occurrence pattern of the protein (E9BCZ9) and its interacting members, seen to be conserved across Eukaryotes.

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References

    1. Alvar J., Croft S. L., Kaye P., Khamesipour A., Sundar S., Reed S.G. (2013). Case study for a vaccine against leishmaniasis. Vaccine 31 Suppl. 2, B244–B249 10.1016/j.vaccine.2012.11.080 - DOI - PubMed
    1. Alvar J., Vélez I.D., Bern C., Herrero M., Desjeux P., Cano J., et al. (2012). “Leishmaniasis Worldwide and Global Estimates of Its Incidence.” Edited by Martyn Kirk. PLoS ONE 7:e35671 10.1371/journal.pone.0035671 - DOI - PMC - PubMed
    1. Anishetty S., Pulimi M., Pennathur G. (2005). Potential drug targets in mycobacterium tuberculosis through metabolic pathway analysis. Comput. Biol. Chem. 29, 368–378 10.1016/j.compbiolchem.2005.07.001 - DOI - PubMed
    1. Ashburner M., Ball C.A., Blake J.A., Botstein D., Butler H., Cherry J. M., et al. (2000). Gene ontology: tool for the unification of biology. Nat. Genet. 25, 25–29 10.1038/75556 - DOI - PMC - PubMed
    1. Bhunia G. S., Kesari S., Chatterjee N., Kumar V., Das P. (2013). Spatial and temporal variation and hotspot detection of kala-azar disease in Vaishali district (Bihar), India. BMC Infect. Dis. 13:64 10.1186/1471-2334-13-64 - DOI - PMC - PubMed

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