Disease relevance of PF11_0162

• Falstatin, expressed in Escherichia coli, was a potent reversible inhibitor of the P. falciparum cysteine proteases falcipain-2 and falcipain-3, as well as other parasite- and nonparasite-derived cysteine proteases, but it was a relatively weak inhibitor of the P. falciparum cysteine proteases falcipain-1 and dipeptidyl aminopeptidase 1 [1].

High impact information on PF11_0162

• Falcipain-2 and falcipain-3 are food vacuole hemoglobinases that may have additional functions [2].
• Compared with the parental strain, resistant parasites showed no changes in multiplication rates, but elevations in cysteine protease activity, falcipain-2 and falcipain-3 copy numbers, transcription of falcipain genes, and levels of these target proteases in trophozoites [3].
• Resistant parasites grown in the absence of the vinyl sulfone for 12 weeks showed partial reversion, with increased inhibitor sensitivity and apparent decreases in copy numbers of falcipain-2 and falcipain-3 [3].
• Optimized compounds inhibited falcipain-2 and falcipain-3, blocked hemoglobin hydrolysis, and prevented the development of P. falciparum at nanomolar concentrations [4].
• We now report the structure-activity relationships for inhibition of falcipain-2, falcipain-3, and parasite development by 39 new vinyl sulfone, vinyl sulfonate ester, and vinyl sulfonamide cysteine protease inhibitors [5].

Biological context of PF11_0162

• The vivapain-2 and vivapain-3 genes predicted papain-family cysteine proteases, which shared a number of unusual features with falcipain-2 and falcipain-3, including large prodomains and short N-terminal extensions on the catalytic domain [6].

Anatomical context of PF11_0162

• Falcipain-2 and falcipain-3 are hemoglobinases that appear to hydrolyse host erythrocyte hemoglobin in the parasite food vacuole [7].

Analytical, diagnostic and therapeutic context of PF11_0162

• Immunoprecipitation of metabolically labeled proteins indicated that falcipain-2 was synthesized through the trophozoite stage, falcipain-3 appeared in late trophozoites/early schizonts, and both proteases persisted for at least 6 h after synthesis [8].
• Among promising new targets for antimalarial chemotherapy are the cysteine protease hemoglobinases falcipain-2 and falcipain-3 [4].

References