title: Molecular characterization of Mtb-OMP decarboxylase by modeling, docking and dynamic studies.
abstract: Tuberculosis (TB), the second most deadly disease in the world is caused by Mycobacterium tuberculosis (Mtb). In the present work a unique enzyme of Mtb orotidine 5' monophosphate decarboxylase (Mtb-OMP Decase) is selected as drug target due to its indispensible role in biosynthesis of pyrimidines. The present work is focused on understanding the structural and functional aspects of Mtb-OMP Decase at molecular level. Due to absence of crystal structure, the 3D structure of Mtb-OMP Decase was predicted by MODELLER9V7 using a known structural template 3L52. Energy minimization and refinement of the developed 3D model was carried out with Gromacs 3.2.1 and the optimized homology model was validated by PROCHECK,WHAT-IF and PROSA2003. Further, the surface active site amino acids were quantified by WHAT-IF pocket. The exact binding interactions of the ligands, 6-idiouridine 5' monophosphate and its designed analogues with the receptor Mtb-OMP Decase were predicted by docking analysis with AUTODOCK 4.0. This would be helpful in understanding the blockade mechanism of OMP Decase and provide a candidate lead for the discovery of Mtb-OMP Decase inhibitors, which may bring insights into outcome new therapy to treat drug resistant Mtb.
authors: Department of Biotechnology, Sri Krishnadevaraya University, Anantapur, 260003, India.
authors: P
authors: P
authors: Madhusudana
authors: B
authors: B
authors: Babajan
authors: M
authors: M
authors: Chaitanya
authors: C M
authors: CM
authors: Anuradha
authors: C
authors: C
authors: Shobharani
authors: Rajasekar
authors: R
authors: Chikati
authors: Chitta Suresh
authors: CS
authors: Kumar
authors: K R S Sambasiva
authors: KR
authors: Rao
authors: Sudhakar
authors: S
authors: Poda
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009964:Orotidine-5'-Phosphate Decarboxylase / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D016415:Sequence Alignment; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D008024:Ligands; D009964:Orotidine-5'-Phosphate Decarboxylase