| 19097788 |
Dong CK, Patel V, Yang JC, Dvorin JD, Duraisingh MT, Clardy J, Wirth DF: Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors. J Biol Chem. 2004 Apr 23;279(17):17197-204. Epub 2004 Feb 11.
Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex I) of many other eukaryotes. Recombinantly expressed pfNDH2 prefers coenzyme CoQ (0) as an acceptor substrate, and can also use the artificial electron acceptors, menadione and dichlorophenol-indophenol (DCIP). Previously characterized NDH2 inhibitors, dibenziodolium chloride (DPI), diphenyliodonium chloride (IDP), and 1-hydroxy-2-dodecyl-4 (1H) quinolone (HDQ) do not inhibit pfNDH2 activity. Here, we provide evidence that HDQ likely targets another P. falciparum mitochondrial enzyme, dihydroorotate dehydrogenase (pfDHOD), which is essential for de novo pyrimidine biosynthesis. |
6(0,0,1,1) |