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Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors.

ABSTRACT: 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.

SUBMITTER: Dong CK

PROVIDER: S-EPMC4422330 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors.

Dong Carolyn K CK Patel Vishal V Yang Jimmy C JC Dvorin Jeffrey D JD Duraisingh Manoj T MT Clardy Jon J Wirth Dyann F DF

Bioorganic & medicinal chemistry letters 20081124 3

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-dodec ...[more]

PMID: 19097788

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