Plasmodium falciparum heme detoxification protein (PfHDP)

Plasmodium falciparum heme detoxification protein (PfHDP) is a critical protein produced by the malaria parasite during its intraerythrocytic stage [1, 3]. As the parasite digests host hemoglobin to obtain amino acids, it releases large amounts of toxic free heme (ferriprotoporphyrin IX) [2]. To survive, the parasite must rapidly detoxify this heme by converting it into an insoluble, chemically inert crystalline pigment called hemozoin [1]. PfHDP acts as a highly efficient catalyst in this biocrystallization process, being significantly more potent than other factors like lipids or histidine-rich proteins [1, 3]. Because this detoxification pathway is unique to the parasite and essential for its survival, it serves as a primary target for several classes of antimalarial drugs, most notably the quinolines [4]. These drugs bind to heme or the growing hemozoin crystals, preventing further polymerization and causing the accumulation of toxic heme, which leads to parasite death through oxidative stress and membrane damage [2, 4, 5]. [1] Jani, D., et al. (2008). PLoS Pathog 4(4): e1000053. [2] Sigala, P. A., & Goldberg, D. E. (2014). Annu Rev Microbiol 68:259-78. [3] UniProtKB - Q8I6K1 (HDP_PLAF7). [4] Sullivan, D. J. (2002). Int J Parasitol 32(13):1645-53. [5] Goldberg, D. E., et al. (1990). J Exp Med 172(6):1743-9.

Other names

HDPHeme-binding proteinMalarial heme detoxification proteinPF3D7_1446800Histidine-rich protein 2PfHRP2Heme-associated proteins

Inhibition of heme biocrystallization into hemozoin, leading to the accumulation of toxic free heme (ferriprotoporphyrin IX) which causes parasite membrane damage and oxidative stress [1, 4].