UNASSIGNED: Atovaquone, a coenzyme Q analogue has been indicated to specifically target the cytochrome bc1 complex of the mitochondrial respiratory chain in the @entity4801 and other protozoan. Various mutations in the quinone binding site of the @entity68216 gene of @entity3964 spp. such as @entity68217 , @entity68218 , @entity68219 , @entity68220 , @entity68221 , @entity68222 , @entity68223 , and @entity68224 are suggesting to associate with resistance to atovaquone. There is no direct evidence of relation between the mutations and resistance to atovaquone in @entity3964 parasite that has been available. Technical difficulties in isolating active assayable mitochondria in the @entity4801 hinder us to obtain direct biochemical evidence to support the relation between the mutations and drug resistance. The establishment of a mitochondrial isolation method for the @entity311 parasite has allowed us to test the degree of resistance of @entity2637 isolates to atovaquone directly. We have tested the activity of dihydroorotate (DHO)-cytochrome c reductase in various @entity2637 atovaquone resistant clones in the presence of a wide concentration range of atovaquone. Our results show the IC50 of @entity2637 atovaquone resistant clones is much higher (1.5 up to 40nM) in comparison to the atovaquone sensitive clones (0.132-0.465nM). The highest IC50 was revealed in clones carrying @entity68221 and @entity68223 mutations (which play an important role in atovaquone resistance in @entity3964 ), with an approximately 100-fold increase. The findings indicate the importance of the mutation in the quinone binding site of the @entity68216 gene and that provide a direct evidence for the atovaquone inhibitory mechanism in the cytochrome bc1 complex of the parasite.

Direct evidence for the atovaquone action on the XXXX cytochrome bc1 complex.

@entity68217 :: ('p|SUB|M|133|I', 'ProteinMutation') :: ['M133I'] @entity68224 :: ('p|SUB|V|284|F', 'ProteinMutation') :: ['V284F'] @entity68218 :: ('p|SUB|L|144|S', 'ProteinMutation') :: ['L144S'] @entity68222 :: ('p|SUB|Y|268|S', 'ProteinMutation') :: ['Y268S'] @entity68219 :: ('p|SUB|L|271|V', 'ProteinMutation') :: ['L271V'] @entity68221 :: ('p|SUB|Y|268|C', 'ProteinMutation') :: ['Y268C'] @entity68216 :: ('2655541(Tax:5833)', 'Gene') :: ['cytochrome b'] @entity68220 :: ('p|SUB|K|272|R', 'ProteinMutation') :: ['K272R'] @entity3964 :: ('5833', 'Species') :: ['Plasmodium falciparum', 'Plasmodium'] @entity4801 :: ('MESH:D010272', 'Disease') :: ['malarial parasite'] @entity311 :: ('MESH:D008288', 'Disease') :: ['malaria'] @entity2637 :: ('5821', 'Species') :: ['Plasmodium berghei', 'P. berghei'] @entity68223 :: ('p|SUB|Y|268|N', 'ProteinMutation') :: ['Y268N']
@entity3964 :: (5833,Species) :: ['Plasmodium']
