Independent amino acid residues in the S2 pocket of falcipain-3 determine its specificity for P2 residues in substrates

Kinetic characterization of a novel cysteine peptidase from the protozoan Babesia bovis, a potential target for drug design

“…4), presented no major proteolytic activity towards Z-RR-AMC and high catalytic efficiency for Z-FR-AMC (Table 2). Moreover, the residue I94 of the S2 pocket of falcipain-3 is responsible for the Leu preference at P2 position [56], therefore the same preference found between BbCp and babesipain-1 (Val > Leu) could be explained by the conservation of the Ser residue at this position (Sup. Fig.…”

“…which would offer a narrower space and preferentially accommodate small residues [29]. However, it was recently demonstrated that the charged residue is responsible for stabilizing a positively charged P2 residue of the substrate and does not interfere with the binding of aromatic or branched side chains from hydrophobic residues [56,57].…”

In Vitro and In Silico Anti‐plasmodial Evaluation of Newly Synthesized β‐Carboline Derivatives

“…FP3 a cysteine protease is a crucial drug target for lethal human malaria. [28] It plays a major role in the degradation of host hemoglobin providing nutrients for nourishment and growth of the parasite. [29] It mostly expressed in the trophozoite stage.…”

Expression of cysteine proteinases and cystatins in parasites and use of cysteine proteinase inhibitors in parasitic diseases. Part III: Protozoa (2): Plasmodium spp.

“…Later, it was found that FP-3 showed similarity to FPs 2 and 2` regarding possession of 1) a specific conserved motif (10 amino acids) near the C terminal of its catalytic domain to bind with hemoglobin prior to degradation [20] ; 2) lysine and phenylalaninevaline motifs in luminal and cytoplasmic portions of its prodomain for efficient trafficking to the food vacuole [26] ; and 3) specific residues contributed to its activity as potent hemoglobinase. Residues substitution showed activity on peptide substrates than wild type FP-3, but was not efficient as hemoglobinase [36] .…”