A Computational Approach towards the Understanding of Plasmodium falciparum Multidrug Resistance Protein 1.

Autor:	Patel SK; Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Ahmedabad 380009, India ; Department of Zoology, Biomedical Technology and Human Genetics, University School of Sciences, Gujarat University, Ahmedabad 380009, India., George LB; Department of Zoology, Biomedical Technology and Human Genetics, University School of Sciences, Gujarat University, Ahmedabad 380009, India., Prasanth Kumar S; Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Ahmedabad 380009, India., Highland HN; Department of Zoology, Biomedical Technology and Human Genetics, University School of Sciences, Gujarat University, Ahmedabad 380009, India., Jasrai YT; Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Ahmedabad 380009, India., Pandya HA; Department of Bioinformatics, Applied Botany Centre (ABC), University School of Sciences, Gujarat University, Ahmedabad 380009, India., Desai KR; Department of Zoology, Biomedical Technology and Human Genetics, University School of Sciences, Gujarat University, Ahmedabad 380009, India.
Jazyk:	angličtina
Zdroj:	ISRN bioinformatics [ISRN Bioinform] 2013 Aug 01; Vol. 2013, pp. 437168. Date of Electronic Publication: 2013 Aug 01 (Print Publication: 2013).
DOI:	10.1155/2013/437168
Abstrakt:	The emergence of drug resistance in Plasmodium falciparum tremendously affected the chemotherapy worldwide while the intense distribution of chloroquine-resistant strains in most of the endemic areas added more complications in the treatment of malaria. The situation has even worsened by the lack of molecular mechanism to understand the resistance conferred by Plasmodia species. Recent studies have suggested the association of antimalarial resistance with P. falciparum multidrug resistance protein 1 (PfMDR1), an ATP-binding cassette (ABC) transporter and a homologue of human P-glycoprotein 1 (P-gp1). The present study deals about the development of PfMDR1 computational model and the model of substrate transport across PfMDR1 with insights derived from conformations relative to inward- and outward-facing topologies that switch on/off the transportation system. Comparison of ATP docked positions and its structural motif binding properties were found to be similar among other ATPases, and thereby contributes to NBD domains dimerization, a unique structural agreement noticed in Mus musculus Pgp and Escherichia coli MDR transporter homolog (MsbA). The interaction of leading antimalarials and phytochemicals within the active pocket of both wild-type and mutant-type PfMDR1 demonstrated the mode of binding and provided insights of less binding affinity thereby contributing to parasite's resistance mechanism.
Databáze:	MEDLINE
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