Open AccessDifferences in biochemical properties of the Plasmodial falcipain‐2 and berghepain‐2 orthologues: Implications for in vivo screens of inhibitors
Author(s) -
Cheryl Chan,
Liuh Ling Goh,
TiowSuan Sim
Publication year - 2005
Publication title -
fems microbiology letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.899
H-Index - 151
eISSN - 1574-6968
pISSN - 0378-1097
DOI - 10.1016/j.femsle.2005.06.024
Subject(s) - plasmodium berghei , plasmodium falciparum , biology , in vivo , cysteine protease , mutagenesis , gene , biochemistry , protease , enzyme , microbiology and biotechnology , genetics , mutation , malaria , immunology
Falcipain‐2A, the cysteine protease of Plasmodium falciparum has been proposed as a good drug target. This study evaluated the suitability of Plasmodium berghei as the animal model and reports the first functional expression and characterization of the falcipain‐2A orthologue, berghepain‐2. Comparative studies revealed that the orthologues exhibited different biochemical properties. Berghepain‐2 demonstrated optimal activity at a narrower pH optima of 5.5–6 and a lack of preference for substrates with leucine at position 2. Mutagenesis studies revealed roles for residues Val63 and Arg230 of berghepain‐2 in contributing to its distinctive biochemical properties. This warrants re‐evaluation of employing P. berghei as the murine model for the in vivo screening of falcipain‐2A inhibitors. More importantly, these findings stress the underlying importance of establishing the functionality of relevant genes of P. falciparum with concomitant relevance to its murine counterpart prior to its use as the animal model for the screening of potential antimalarials.