(3R)-hydroxyacyl-acyl carrier protein dehydratase (FabZ) (FabZ)

(3R)-hydroxyacyl-acyl carrier protein dehydratase, commonly referred to as FabZ, is an essential enzyme within the Type II fatty acid synthesis (FAS II) pathway of Plasmodium parasites, such as Plasmodium falciparum (UniProt: Q8I0S1). This enzyme is localized in the apicoplast, a relict plastid organelle unique to Apicomplexan parasites, where it catalyzes the dehydration of (3R)-hydroxyacyl-ACP to trans-2-enoyl-ACP during the fatty acid elongation cycle (PubMed: 15590638). Because humans utilize a structurally distinct Type I fatty acid synthase (FAS I) system, FabZ represents a highly selective therapeutic target for antimalarial drug development with minimal risk of cross-reactivity with host enzymes (PubMed: 19413314). Inhibition of FabZ disrupts the production of essential fatty acids required for the formation of the parasite's membranes, particularly during the liver stage and potentially the erythrocytic stage of the life cycle. Various small molecules, including natural flavonoids like luteolin and synthetic compounds such as NAS-91, have been identified as potent inhibitors that arrest parasite growth by binding to the enzyme's active site (PubMed: 17606610). These interactions prevent the completion of the fatty acid chain, leading to parasite death and offering a promising avenue for overcoming resistance to current antimalarial therapies.

Other names

Beta-hydroxyacyl-ACP dehydratase3-hydroxyacyl-ACP dehydratasePfFabZBeta-hydroxyacyl-acyl carrier protein dehydratase

Inhibition of the dehydration of (3R)-hydroxyacyl-ACP to trans-2-enoyl-ACP in the fatty acid synthesis II (FAS II) pathway