2021
DOI: 10.1038/s42003-021-02442-1
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A fragment-based approach identifies an allosteric pocket that impacts malate dehydrogenase activity

Abstract: Malate dehydrogenases (MDHs) sustain tumor growth and carbon metabolism by pathogens including Plasmodium falciparum. However, clinical success of MDH inhibitors is absent, as current small molecule approaches targeting the active site are unselective. The presence of an allosteric binding site at oligomeric interface allows the development of more specific inhibitors. To this end we performed a differential NMR-based screening of 1500 fragments to identify fragments that bind at the oligomeric interface. Subs… Show more

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Cited by 7 publications
(1 citation statement)
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“…It controls erythrocyte invasion and virulence in the Plasmodium parasite [ 72 ] 39 Histone deacetylase It catalyzes the deacetylation of acetylated histones leading to transcriptional repression [ 71 ] 40 Hypoxanthine guanine phosphoribosyl transferase Helps in DNA/RNA synthesis via de novo synthesis [ 73 ] 41 Lactate dehydrogenase The critical enzyme of energy production. It catalyzes the interconversion of pyruvate to lactate in the glycolysis process [ 74 ] 42 Malate dehydrogenase It involves NADH and citrate production to support the TCA cycle, ETC [ 75 ] 43 Malatequinone oxidoreductase Membrane protein. Involved in three essential pathways (ETC, TCA, and fumarate cycle) [ 76 ] 44 Merozoite surface protein-1 Essential for the attachment of merozoites to host receptor.…”
Section: Introductionmentioning
confidence: 99%
“…It controls erythrocyte invasion and virulence in the Plasmodium parasite [ 72 ] 39 Histone deacetylase It catalyzes the deacetylation of acetylated histones leading to transcriptional repression [ 71 ] 40 Hypoxanthine guanine phosphoribosyl transferase Helps in DNA/RNA synthesis via de novo synthesis [ 73 ] 41 Lactate dehydrogenase The critical enzyme of energy production. It catalyzes the interconversion of pyruvate to lactate in the glycolysis process [ 74 ] 42 Malate dehydrogenase It involves NADH and citrate production to support the TCA cycle, ETC [ 75 ] 43 Malatequinone oxidoreductase Membrane protein. Involved in three essential pathways (ETC, TCA, and fumarate cycle) [ 76 ] 44 Merozoite surface protein-1 Essential for the attachment of merozoites to host receptor.…”
Section: Introductionmentioning
confidence: 99%