Nitroimidase Lab Report

Docking studies of Nitroimidazo-oxazine with Pyridoxine 5'-Phosphate Oxidase
M Sathish kumar1 , UCA Jaleel2
CSIR OSDD Research Unit , Bangalore
Abstract

Mycobacterium tuberculosis continues to be one of the world’s most debilitating and deadly pathogens. PA-824 is a nitroimidazole that has demonstrated bactericidal and sterilizing activity against drug-resistant and non drug-resistant tuberculosis. PA-824 is activated by either a bacterial enzyme or a cofactor, which is a compound that binds to a protein. This prodrug was used as a ligand to bind with the protein PDB ID:1XXO (Pyridoxine 5'-phosphate oxidase complexed with pyridoxal 5'-phosphate). Pyridoxine 5-phosphate oxidase is the enzyme that catalyzes the rate limited step of the

Like OPC-67683, Nitroimidazo-oxazine is a nitroimidazole that has demonstrated bactericidal and sterilizing activity against drug-resistant and non drug-resistant TB. Nitroimidazo-oxazine has also shown activity against both active and latent TB. In a 2002 agreement with the former biotechnology company Chiron, The TB Alliance is carrying out phase II clinical testing on Nitroimidazo-oxazine (Diacon et al. ). Nitroimidazo oxaine is also active against latent TB bacteria .In a latent state, bacteria are anaerobic and else replicating very slowly and non replicating. In 2008 researchers from the national Institute of allergy and Infectious Diseases found that Nitroimizado oxaine kills latent bacteria by releasing a gas called nitric oxide , which poisons the bacteria . Nitroimizado oxaine mimics the body’s natural immune response ,but it is more specific and only releases the gas upon entering the tuberculosis

Docking Protocol

The docking calculation was executed by using Autodock 4.0 . Grid maps with 60*60*60 points were made and the grid point spacing of 0.375 angstroms. The best conformation was chosen with the lower docking energy. Cygwin is used for to execute the autogrid and autodock files . The Binding interaction of complex pyridoxine 5 phosphate oxidase – Nitroimidazooxaine conformations including hydrogen bond and the bond length are analyse by chimera software.

3. Result and Disscussion

Docking AnalysisResult :

Pyridoxine 5 Phosphate oxidase ,, the macromolecule and the ligand molecule were subject to docking analysis by using Autodock 4.2 .Molecular docking simulations were conducted with this software 10 docking runs were performed. Gird parameter were set as mentioned earlier and the grid spacing point was 0.375 angstoms . After the simulations were complete ,the docked structures were analyzed and the interactions were seen. Hydrogen bond interactions and the binding energy between the protein and ligand molecule are