Structure Modeling of Human TyrosylDNA Phosphodiesterase 1 and Screening for Its Inhibitors
| Autor: | D. K. Nilov, Olga I. Lavrik, Vytas K. Švedas, Alexandra L. Zakharenko, I. V. Gushchina |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Phosphotyrosine binding biology Molecular model Oligonucleotide Chemistry Stereochemistry Phosphodiesterase Active site Tyrosyl-DNA Phosphodiesterase 1 Biochemistry Molecular mechanics 03 medical and health sciences 030104 developmental biology Docking (molecular) biology.protein Molecular Medicine Molecular Biology Biotechnology |
| Zdroj: | Acta Naturae. 9:59-66 |
| ISSN: | 2075-8251 |
| Popis: | The DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) represents a potential molecular target for anticancer therapy. A human Tdp1 model has been constructed using the methods of quantum and molecular mechanics, taking into account the ionization states of the amino acid residues in the active site and their interactions with the substrate and competitive inhibitors. The oligonucleotide- and phosphotyrosine-binding cavities important for the inhibitor design have been identified in the enzymes active site. The developed molecular model allowed us to uncover new Tdp1 inhibitors whose sulfo group is capable of occupying the position of the 3-phosphate group of the substrate and forming hydrogen bonds with Lys265, Lys495, and other amino acid residues in the phosphotyrosine binding site. |
| Databáze: | OpenAIRE |
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