IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS) e-ISSN: 2278-3008, p-ISSN:2319-7676. Volume 8, Issue 5 (Nov. – Dec. 2013), PP 82-93 www.iosrjournals.org www.iosrjournals.org 82 | Page Homology Modeling and characterization of Phosphoenolpyruvate Carboxykinase (PEPCK) from Schistosoma japonicum Akalesh Kumar Verma* 1 , Purobi Nath 2 , Surya Bali Prasad 1 , Devid Kardong 3 , Jashodeb Arjun 4 , Durba Kashyap 4 and Ramesh Chillawar 5 1 Cell and Tumor Biology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong-793022, India. 2 Parasitology & Ethnopharmacology Laboratory, Department of Zoology, North-Eastern Hill University, Shillong-793022, India. 3 Depment of Life Sciences, Dibrugarh University, Dibrugarh- 786004, India. 4 Department of Zoology, Biochemistry Division, Lumding College, Lumding-782447, Assam, India. 5 Department of Botany, Yeshwant Mahavidalaya Nanded (Maharashtra) - 431602, India. Abstract: Phosphoenolpyruvate carboxykinase (PEPCK), a carboxylase enzyme is present in all living organisms. It catalyzes metal-nucleotide coupled reversible decarboxylation and phosphorylation between phosphoenolpyruvate (PEP) and oxaloacetate (OAA) depending on the system and the availability of the intermediates. In fungi, plants and in most bacteria, production of PEP from OAA by PEPCK is the key step during gluconeogenesis. In healthy human cytosolic PEPCK enzyme is present only during glucose starvation; cytosolic PEPCK rapidly disappears on the replenishment of glucose due to hormonal control of the transcription of the cytosolic PEPCK- gene. In some parasitic helminthes like Ascaris suum, nematodes such as Haemonchus contortus, PEPCK carry out the reverse reaction to produce OAA from PEP. In Trypanosoma cruzi and all species of the genus Leishmania, this enzyme is very active even in the presence of high level of carbohydrate. There is a significant functional difference between parasitic PEPCK and mammalian host PEPCK. These differences between the mammalian host and the parasite enzyme strongly support the belief that PEPCK should be further investigated as a possible target for selective chemotherapeutic agents. The experimental 3D structure of PEPCK of Schistosoma japonicum is not available in protein data bank. Therefore, based on the knowledge of the best template (3DT7), model of 3D structure of Schistosoma japonicum PEPCK was prepared using Modeller v9.10 software and processed in to energy minimization, Ramachandran plot analysis, quality assessment and characterization. Keywords: Antihelminthic, Docking, Homology modeling, Schistosoma japonicum, Phosphoenolpyruvate carboxykinase I. INTRODUCTION Phosphoenolpyruvate carboxykinase (PEPCK) is the key enzyme to initiate the gluconeogenic pathway in vertebrates, yeast, plants and most bacteria. Nucleotide specificity divided all PEPCK into two groups. All eukaryotic and most archaeal PEPCK are GTP-dependent. Bacterial and fungal PEPCK can be either ATP-or GTP-specific but all plant PEPCK are ATP specific [1]. Amino acid sequence alignment of PEPCK enzymes shows that the nucleotide binding sites are somewhat conserved within each class with few exceptions that do not have any clear ATP- or GTP-specific binding motif. Although the active site residues are mostly conserved in all PEPCK, not much significant sequence homology persists between ATP and GTP dependent PEPCK enzymes. There is only one planctomycetes PEPCK enzyme (from Cadidatus Kuenenia stuttgartiensis) that shows sequence homology with both ATP-and GTP-dependent PEPCK [1]. ATP-utilizing PEPCKs are monomers or oligomers of identical subunits found in certain bacteria, yeast, trypanosomatids, and plants, while GTP-utilizing PEPCK are mainly monomers found in animals and some bacteria. Both require divalent cations for activity, such as magnesium or manganese. One cation interacts with the enzyme at metal binding site-1 to elicit activation, while the second cation interacts at metal binding site-2 to serve as a metal-nucleotide substrate. Natural products comprising plants, animals and minerals have been the basis for treatment of human diseases in traditional medicine by indigenous peoples, throughout the world and across time, is a well documented practice [2], [3], [4]. At the same time molecular modeling and docking have recently been introduced and gained attention among medicinal chemists [5]. It is believed that most of the chemotherapeutic agents directly or indirectly alter enzyme systems of helminth parasites mainly PEPCK [6], [7] and serves as a good antihelminthic agents. A limited choice of safe and efficacious drugs is currently available for the