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Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine
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| Zeitschriftentitel: | International Journal of Molecular Sciences |
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| Personen und Körperschaften: | , , , , , , , , , , |
| In: | International Journal of Molecular Sciences, 21, 2020, 6, S. 2159 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
MDPI AG
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| Schlagwörter: |
| author_facet |
Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. |
|---|---|
| author |
Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. |
| spellingShingle |
Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. International Journal of Molecular Sciences Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| author_sort |
nilov, dmitry |
| spelling |
Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms21062159 <jats:p>7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as a potential anticancer drug candidate. Here we describe a study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 and nucleosomal DNA. It is shown that 7-MG competes with substrate NAD+ and its binding in the PARP-1 active site is mediated by hydrogen bonds and nonpolar interactions with the Gly863, Ala898, Ser904, and Tyr907 residues. 7-MG promotes formation of the PARP-1–nucleosome complexes and suppresses DNA-dependent PARP-1 automodification. This results in nonproductive trapping of PARP-1 on nucleosomes and likely prevents the removal of genotoxic DNA lesions.</jats:p> Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine International Journal of Molecular Sciences |
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| title |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_unstemmed |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_full |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_fullStr |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_full_unstemmed |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_short |
Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_sort |
molecular mechanisms of parp-1 inhibitor 7-methylguanine |
| topic |
Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| url |
http://dx.doi.org/10.3390/ijms21062159 |
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2020 |
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2159 |
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<jats:p>7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as a potential anticancer drug candidate. Here we describe a study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 and nucleosomal DNA. It is shown that 7-MG competes with substrate NAD+ and its binding in the PARP-1 active site is mediated by hydrogen bonds and nonpolar interactions with the Gly863, Ala898, Ser904, and Tyr907 residues. 7-MG promotes formation of the PARP-1–nucleosome complexes and suppresses DNA-dependent PARP-1 automodification. This results in nonproductive trapping of PARP-1 on nucleosomes and likely prevents the removal of genotoxic DNA lesions.</jats:p> |
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| author | Nilov, Dmitry, Maluchenko, Natalya, Kurgina, Tatyana, Pushkarev, Sergey, Lys, Alexandra, Kutuzov, Mikhail, Gerasimova, Nadezhda, Feofanov, Alexey, Švedas, Vytas, Lavrik, Olga, Studitsky, Vasily M. |
| author_facet | Nilov, Dmitry, Maluchenko, Natalya, Kurgina, Tatyana, Pushkarev, Sergey, Lys, Alexandra, Kutuzov, Mikhail, Gerasimova, Nadezhda, Feofanov, Alexey, Švedas, Vytas, Lavrik, Olga, Studitsky, Vasily M., Nilov, Dmitry, Maluchenko, Natalya, Kurgina, Tatyana, Pushkarev, Sergey, Lys, Alexandra, Kutuzov, Mikhail, Gerasimova, Nadezhda, Feofanov, Alexey, Švedas, Vytas, Lavrik, Olga, Studitsky, Vasily M. |
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| description | <jats:p>7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as a potential anticancer drug candidate. Here we describe a study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 and nucleosomal DNA. It is shown that 7-MG competes with substrate NAD+ and its binding in the PARP-1 active site is mediated by hydrogen bonds and nonpolar interactions with the Gly863, Ala898, Ser904, and Tyr907 residues. 7-MG promotes formation of the PARP-1–nucleosome complexes and suppresses DNA-dependent PARP-1 automodification. This results in nonproductive trapping of PARP-1 on nucleosomes and likely prevents the removal of genotoxic DNA lesions.</jats:p> |
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| spelling | Nilov, Dmitry Maluchenko, Natalya Kurgina, Tatyana Pushkarev, Sergey Lys, Alexandra Kutuzov, Mikhail Gerasimova, Nadezhda Feofanov, Alexey Švedas, Vytas Lavrik, Olga Studitsky, Vasily M. 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms21062159 <jats:p>7-Methylguanine (7-MG), a natural compound that inhibits DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1), can be considered as a potential anticancer drug candidate. Here we describe a study of 7-MG inhibition mechanism using molecular dynamics, fluorescence anisotropy and single-particle Förster resonance energy transfer (spFRET) microscopy approaches to elucidate intermolecular interactions between 7-MG, PARP-1 and nucleosomal DNA. It is shown that 7-MG competes with substrate NAD+ and its binding in the PARP-1 active site is mediated by hydrogen bonds and nonpolar interactions with the Gly863, Ala898, Ser904, and Tyr907 residues. 7-MG promotes formation of the PARP-1–nucleosome complexes and suppresses DNA-dependent PARP-1 automodification. This results in nonproductive trapping of PARP-1 on nucleosomes and likely prevents the removal of genotoxic DNA lesions.</jats:p> Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine International Journal of Molecular Sciences |
| spellingShingle | Nilov, Dmitry, Maluchenko, Natalya, Kurgina, Tatyana, Pushkarev, Sergey, Lys, Alexandra, Kutuzov, Mikhail, Gerasimova, Nadezhda, Feofanov, Alexey, Švedas, Vytas, Lavrik, Olga, Studitsky, Vasily M., International Journal of Molecular Sciences, Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| title | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_full | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_fullStr | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_full_unstemmed | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_short | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| title_sort | molecular mechanisms of parp-1 inhibitor 7-methylguanine |
| title_unstemmed | Molecular Mechanisms of PARP-1 Inhibitor 7-Methylguanine |
| topic | Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| url | http://dx.doi.org/10.3390/ijms21062159 |