Phylogenetic Analysis and Protein Modeling of Plasmodium falciparum Aspartate Transcarbamoylase (ATCase)

Sulaiman Depamede, Ian Menz

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    1 Citation (Scopus)

    Abstract

    Unlike most mammalian cells, Plasmodium sp., are unable to utilize preformed pyrimidine bases and nucleosides hence they are reliant solely on de novo pathway. Aspartate transcarbamoylase (ATCase, EC 2.1.3.2) catalyzes the first committed step in de novo pyrimidine biosynthesis pathway, is a potential target for novel anti-parasitic including antimalarial drugs. P. falciparum ATCase has not been studied extensively. To reveal whether it has a regulatory subunit or no and how its evolution, phylogenetic analysis and protein modeling of ATCase P. falciparum were studied. The structural model can be used to identify the possible differences between active sites of mammalian and Plasmodium enzyme. This is important in a relation with antimalarial drug development. Analogous sequences from P. falciparum were searched by 'tBLASTn search' carried out using the web based tools provided by National Center for Biotechnology Information (NCBI). After alignment of ATCase residues sequences, phylogram was constructed by means of MEGA 2.1 software. The results show that the residues sequences of P. falciparum ATCase in the phylogenetic tree constructed clearly positioned P. falciparum as Class C or "A" consistent with Wild and Wales structural organization. In addition the models for the three dimensional protein structures of the catalytic domain of human and P. falciparum ATCase were also generated. As far as our concerned, our study was the first to reveal of P. falciparum ATCase classification based on its ATCase amino acid sequences. However, the structure of P. falciparum ATCase needs to be determined experimentally to confirm this and to assist the rational design of antimalarial drugs.

    Original languageEnglish
    Pages (from-to)599-608
    Number of pages10
    JournalResearch Journal of Microbiology
    Volume6
    Issue number7
    DOIs
    Publication statusPublished - 2011

    Keywords

    • ATCase
    • Biosynthesis
    • N-(phosphonoacetyl)-L-aspartate (PALA)
    • Phylogenetic
    • Plasmodium falciparum
    • Protein modeling
    • Pyrimidine

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