International centre for genetic engineering and biotechnology, Aruna Asaf Marg, New Delhi, India.
Malaria is still one of the deadly disease resulting in the death of million of people worldwide and situation has become worse due to antimalarial drug resistance. The availability of the Plasmodium genome has been instrumental in identifying various cell cycle regulators including several cyclins and cyclin dependent kinases (CDKs). Cyclins are key molecules regulating the activity of CDKs which play an important role in cell cycle regulation. Here we present the in silico characterization of tertiary structural model of pfcyc-1, a cyclin homolog, in an attempt to identify key regions that contribute to pfcyc-1 structure and function. In this study, we predicted the three dimensional structure of pfcyc-1 which is then subjected to molecular dynamic simulation for 10 ns in order to allow this pfcyc-1 to attain stable conformation. One of the significant findings of the study suggests that despite low sequence identity to other characterized cyclins, three-dimensional model of pfcyc-1 possess two five-helix bundles similar to cyclin H and cyclin A. The region corresponding to residue 46-142 of pfcyc-1 has maximum structural homology with cyclin fold cyclin H and cyclin A along with some conserved residues important in mediating cyclin-CDK interaction in known cyclins. The present work may help in gaining deeper insight into the underlying mechanism of CDKs regulation by cyclin in Plasmodium falciparum. Read More ..