Inhibition kinetics of Plasmodium Lactate Dehydrogenase with herbal extracts suggest possible enzyme inhibitor molecular interaction

Abstract

Background Resistance acquired by Plasmodium species (especially P. falciparum )t o most of the present antimalarial drugs is the principal hindrance in controlling malaria. Thus, one of the major challenges towards elimination of Malaria is development of novel and sustainable antimalarial drugs. In this milieu, herbs traditionally used to treat malaria are promising repertoires of antimalarial drugs. Earlier, lab studies have reported selective inhibition of P. falciparum and P. vivax specific Lactate Dehydrogenase (PfLDH and PvLDH) by Phyllanthus amarus aqueous extract and Murraya koenigii chloroform extract respectively. In the present investigation, we studied inhibition kinetics of PfLDH and PvLDH to explore molecular interactions between enzyme and inhibitor. Materials and methods Recombinant PfLDH and PvLDH, expressed in E. coli, were used in enzyme assay. LDH activity was measured in the direction of pyruvate to L-lactate conversion [1]. Steady state kinetic constants for substrate and cofactor as well as inhibition constants for plant extracts were measured by double reciprocal plot (Lineweaver and Burk plot). The enzyme inhibitor interactions were determined based on variations in the kinetic constants in presence of inhibitors, compared to control. Results Enzyme inhibition kinetics results are summarised in Table 1. Conclusion