Please use this identifier to cite or link to this item:
|Title:||Homology modeling and mutagenesis analyses of Plasmodium falciparum falcipain 2A: Implications for rational drug design|
Rational drug design
|Citation:||Goh, L.L., Sim, T.S. (2004). Homology modeling and mutagenesis analyses of Plasmodium falciparum falcipain 2A: Implications for rational drug design. Biochemical and Biophysical Research Communications 323 (2) : 565-572. ScholarBank@NUS Repository.|
|Abstract:||The hemoglobin-degrading cysteine proteases falcipains of the malaria parasite Plasmodium falciparum are regarded as potential drug targets. Despite their obvious importance in the virulence of malaria, these proteases remain poorly characterized at the structural levels. Using a bioinformatic and site-directed mutagenesis approach, residues essential for the structure and function of FP2A are elucidated in this study. In total, nine mutants of FP2A were constructed to test the proposed importance of seven different amino acid residues. These recombinant protease mutants were solubly expressed in Escherichia coli and purified by affinity chromatography for enzymatic assessments. Notably, substitutions at positions C99 and C119 induce structural alterations and led to significant reduction in enzyme activity (>97%). The analyses also validated the role of the active triad comprising of C42, H174, and N204 in catalysis and identified a serine at position 149 which is required for specific peptide substrate interactions. The parasite-specific residues, C99, C119, and S149, represent potential sites for differential targeting, since the corresponding residues are absent in the human host's isozymes. © 2004 Elsevier Inc. All rights reserved.|
|Source Title:||Biochemical and Biophysical Research Communications|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 26, 2018
WEB OF SCIENCETM
checked on Dec 24, 2018
checked on Feb 2, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.