Structural characterization of pfSerine hydroxymethyltransferase: A novel target for malaria
Rajasekhar Chikati, C. M. Anuradha, MVNL Chaitanya, Banaganapalli Babajan, Padmanabhan Prasad, Chitta Suresh Kumar · Journal of Bioinformatics and Sequence Analysis · 2010
New chemotherapeutic targets are urgently required to control malaria, a tropical disease caused by Plasmodium sp., which has been haunting mankind for ages. Serine hydroxymethyltransferase (SHMT) plays a major role in DNA biosynthesis.PfSHMT sequence compared for identities with hu mtSHMT (2A7V), T.ThHb8SHMT (2DKJ) and Rabbit cytSHMT (1EQB). ClustralW and Modeller9v3 were used for multiple sequence alignment and homology modeling of PfSHMTrespectively. Validation of the stereochemical quality and structure analysis for the developed PfSHMT model were done with PROCHECK and WHATIF programs. The Z-score as determined by ProSA web analysis. The catalytic residues were Aspartic acid-208, histidine-129, 132, 211, lysine-237, threonine-234, which were conserved in the developed model of SHMT of Plasmodium falciparum. The developed PfSHMT model submitted to PMDB has been accepted with less than 3% stereochemical check failures. The present study would provide valuable information for search and rational drug design of new generation of wide spectrum of novel antimalarial drugs. Key words: Malaria, PfSHMT, DNA biosynthesis, homology modeling, modeller9v3, potential targets.