International Journal of Drug Discovery

11-16

Authors: Koteswara Reddy G., Mohan Kalyan Reddy K., Nagamalleswara Rao K., Gyana R.Satpathy

The bacteria Clostridium botulinum causing botulism. Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin, which is produced by the bacterium Clostridium botulinum.CDP-diacylglycerol-serine O-phosphatidyltransferase is an enzyme that catalyzes the CDP-diacylglycerol, L-serine and produce Cytidine monophosphate (CMP), (3-snphosphatidyl)- L-serine in Clostridium botulinum. CMP is a nucleotide that is helpful in RNA synthesis in Clostridium botulinum.The objective of enzyme inhibition needs structural characterization from its 3-D structure in rational structure based drug design. Homology modeling can produce high-quality structural models when the target and templates are closely related. MODELLER is the program used for homology modeling which provides accurate and efficient models to build loops and side chains found non-identical in sequence. It implements comparative protein structure modeling by satisfaction of spatial restraints. The stereo chemical quality of a best model is validated by PROCHECK server with 86.2% residues under favored region from Ramachandran plot. The CASTp is used for locating, delineating and measuring concave surface regions on three-dimensional structures of proteins. The residues are identified in burial cavity of the best model as Leu (131,141,156), Ala (132), Ile (138,142), Asn (145), Thr (149,153), and Gly (151) with hydrophobic nature. These include pocket located on protein surfaces and voids buried in the interior of proteins that are frequently associated with binding events. Thus present studies of modeling of CDP-diacylglycerol-serine O-phosphatidyltransferas enzyme has brought future prospective to fight against botulism disease and provide better health standaaards for community.

20-50

Authors: Kranthi Raj K., Pathak L.P., Muttineni Ravikumar, Ramachandrana D.

Leukotriene A4 hydrolase (LTA4H) is a hydrolase with a bifunctional zinc enzyme, which plays a role in inflammation. LTA4H may also play an important role in carcinogenesis, especially chronic inflammation-associated carcinogenesis. In this study, chemical feature based pharmacophore models based on 22 currently available LTA4H inhibitors have been developed with the aid of HipHop and HypoRefine modules within Catalyst program package. 3D pharmacophore model developed was, characterized by distinct chemical features such as Hydrogen-bond acceptor (HA), Hydrogen-bond donor (HD), Hydrophobic aliphatic (HPAli), Hydrophobic aromatic (HPAr) that are found to be responsible for the activity of the LTA4H inhibitors. The correlation coefficient, root mean square deviation and cost difference were 0.92, 1.0867 and 53.62 respectively, suggesting that a highly predictive pharmacophore model was successfully obtained. The results of our study provide a valuable tool in designing new leads with desired biological activity for virtual screening.