Homology modeling and docking studies of phosphoenolpyruvate carboxykinase in Schistosoma mansoni

Phosphoenolpyruvate carboxykinase (PEPCK) is an important catalytic enzyme in helminth parasites that catalyses a reverse reaction forming oxaloacetate from phosphoenolpyruvate. Because of its functional significance, present work was undertaken to construct and validate the 3D structure of PEPCK in Schistosoma mansoni. The 3D model protein was generated based on the known crystal structure of rat cytosolic PEPCK as template using Modeller 9v10 software. The resulting models were assessed by Procheck, Anolea, ProSA-web, and Errat. We have also identified all the pockets and voids on the best model protein to provide a detailed delineation of all atoms participating in their formation using CASTp server and to dock with best fitted ligand (guanosine diphosphate, GDP) using AutoDock 4.2. The model protein showed reliable structure with Ramachandran plot: 90.2 % core region, 9.1 % allow, 0.8 % generously allowed and 0.0 % disallowed region amino acid distributions. GDP was found to be docked in its active site, which formed a single H-bond with ASN 524 residue of model protein. Characterisation of PEPCK model protein has also been done to know its various biochemical natures. Therefore, the model structure could prove useful in further functional characterization and may be used to target and design drugs against S. mansoni.