title: Novel point mutations in sulfadoxine resistance genes of Plasmodium falciparum from India.
abstract: Point mutations in the dhfr and dhps genes of Plasmodium falciparum are associated with pyrimethamine and sulfadoxine resistance respectively. In this study we have analyzed these genes from Bikaner (situated in North-West region of India), where both uncomplicated and severe manifestations of P. falciparum malaria are seen. A majority of isolates showed double mutant allele for DHFR. In contrast, the only reported mutation present in DHPS was A437G in few isolates. In addition, three novel non-synonymous mutations were observed in the PfDHPS from this region viz., S587F, N666K and C668W. The mutations at the 666 and 668 codon seem to form a bend in the big loop region of the DHPS enzyme and may affect the binding of the drug to the enzyme. Molecular docking of sulfadoxine to this mutated structure indicates reduction in its binding affinity to this enzyme.
authors.affiliation: Centre for Biotechnology, Biological Sciences Group, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Garg
authors.forename: Vishal
authors.initials: V
authors.lastname: Saxena
authors.forename: Swarna
authors.initials: S
authors.lastname: Kanchan
authors.forename: Pooja
authors.initials: P
authors.lastname: Sharma
authors.forename: Siddharth
authors.initials: S
authors.lastname: Mahajan
authors.forename: Dhanpat
authors.initials: D
authors.lastname: Kochar
authors.forename: Ashis
authors.initials: A
authors.lastname: Das
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D016054:DNA, Protozoan; D004094:Dihydropteroate Synthase / Q000235:genetics; D004351:Drug Resistance; D006801:Humans; D007194:India; D016778:Malaria, Falciparum / Q000469:parasitology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013413:Sulfadoxine / Q000494:pharmacology*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics
chemical_list: D000962:Antimalarials; D016054:DNA, Protozoan; D015800:Protozoan Proteins; D013413:Sulfadoxine; D013762:Tetrahydrofolate Dehydrogenase; D004094:Dihydropteroate Synthase