Homology modeling, molecular dynamics and inhibitor binding study on MurD ligase of Mycobacterium tuberculosis
| Autor: | C. Gopi Mohan, Parameswaran Saravanan, Vivek Kumar, Akanksha Arvind |
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| Rok vydání: | 2011 |
| Předmět: |
chemistry.chemical_classification
DNA ligase Sequence Homology Amino Acid Stereochemistry Molecular Sequence Data Glutamic Acid Health Informatics Mycobacterium tuberculosis Biology Molecular Dynamics Simulation biology.organism_classification General Biochemistry Genetics and Molecular Biology Computer Science Applications Amino acid chemistry.chemical_compound Protein structure chemistry Biochemistry Docking (molecular) Peptidoglycan Homology modeling Amino Acid Sequence Peptide Synthases Peptide sequence Mycobacterium |
| Zdroj: | Interdisciplinary sciences, computational life sciences. 4(3) |
| ISSN: | 1867-1462 |
| Popis: | The cell wall of mycobacterium offers well validated targets which can be exploited for discovery of new lead compounds. MurC-MurF ligases catalyze a series of irreversible steps in the biosynthesis of peptidoglycan precursor, i.e. MurD catalyzes the ligation of D-glutamate to the nucleotide precursor UMA. The three dimensional structure of Mtb-MurD is not known and was predicted by us for the first time using comparative homology modeling technique. The accuracy and stability of the predicted Mtb-MurD structure was validated using Procheck and molecular dynamics simulation. Key interactions in Mtb-MurD were studied using docking analysis of available transition state inhibitors of E.coli-MurD. The docking analysis revealed that analogues of both L and D forms of glutamic acid have similar interaction profiles with Mtb-MurD. Further, residues His192, Arg382, Ser463, and Tyr470 are proposed to be important for inhibitor-(Mtb-MurD) interactions. We also identified few pharmacophoric features essential for Mtb-MurD ligase inhibitory activity and which can further been utilized for the discovery of putative antitubercular chemotherapy. |
| Databáze: | OpenAIRE |
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