Abstract
S-adenosyl-L-homocysteine hydrolase of Plasmodium falciparum (PfSAHH) is a potential drug target against malaria, and selective inhibition of PfSAHH is the excellent strategy to prevent the growth of parasite inside the host. Therefore, a comparative analysis of human S-adenosyl-L-homocysteine hydrolase (HsSAHH) and PfSAHH has been performed to explore the structural differences. Structural superimposition of PfSAHH and HsSAHH has generated the RMSD of 0.749 Å over 394 alpha carbon pairs. Residues of PfSAHH from position Tyr152 to Lys193 aligned with insertion/deletion region in HsSAHH, and these extra residues results in an extent of variation in cavity region of PfSAHH. Nicotinamide adenine dinucleotide (NAD) was observed to form hydrogen bonding with Thr201, Thr202, Thr203, Asn235, Val268, Glu287, Asn322, Ile343, Asn391, Lys473, and Tyr477 and also forms hydrophobic interactions with Val268, Ile288, and Thr320 of PfSAHH. In comparison to HsSAHH, Asn322, Lys473, and Tyr477 residues of PfSAHH are unique in interaction with NAD. 2-Fluoroaristeromycin and other analogues of aristeromycin have shown the good binding affinity for both enzymes. Structural differences between PfSAHH and HsSAHH might be employed to design the potential inhibitor of PfSAHH. To find the target enzyme responsible for an anti-malarial effect, molecular docking and interaction analysis of curcumin were performed with 34 drug targets of P. falciparum. Curcumin shows high affinity for binding with HGPRT of PfHGPRT, and an anti-malarial effect of curcumin might be due to binding with PfHGPRT.
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