Virtual screening of selective inhibitors of phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis
| Autor: | Inna P. Kuranova, D. D. Sidorov-Biryukov, D. D. Podshivalov, Vladimir I. Timofeev |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
chemistry.chemical_classification Virtual screening biology Stereochemistry Active site General Chemistry Condensed Matter Physics biology.organism_classification Mycobacterium tuberculosis 03 medical and health sciences 030104 developmental biology Enzyme chemistry Biochemistry Docking (molecular) biology.protein Phosphopantetheine adenylyltransferase General Materials Science Target protein |
| Zdroj: | Crystallography Reports. 62:405-410 |
| ISSN: | 1562-689X 1063-7745 |
| DOI: | 10.1134/s106377451703018x |
| Popis: | Bacterial phosphopantetheine adenylyltransferase from Mycobacterium tuberculosis (PPAT Mt) is a convenient target protein for the directed search for selective inhibitors as potent antituberculosis drugs. Four compounds suitable for the detailed investigation of their interactions with PPAT Mt were found by virtual screening. The active-site region of the enzyme was chosen as the ligand-binding site. The positions of the ligands found by the docking were refined by molecular dynamics simulation. The nearest environment of the ligands, the positions of which in the active site of the enzyme were found in a computational experiment, was analyzed. The compounds under consideration were shown to directly interact with functionally important active-site amino-acid residues and block access of substrates to the active site. Therefore, these compounds can be used for the design of selective inhibitors of PPAT Mt as potent antituberculosis drugs. |
| Databáze: | OpenAIRE |
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