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Molecular mechanisms of PARP-1 inhibitor 7-methylguanine. / Nilov, Dmitry; Maluchenko, Natalya; Kurgina, Tatyana et al.

In: International Journal of Molecular Sciences, Vol. 21, No. 6, 2159, 03.2020.

Research output: Contribution to journal › Article › peer-review

Harvard

Nilov, D, Maluchenko, N, Kurgina, T, Pushkarev, S, Lys, A, Kutuzov, M, Gerasimova, N, Feofanov, A, Švedas, V, Lavrik, O & Studitsky, VM 2020, 'Molecular mechanisms of PARP-1 inhibitor 7-methylguanine', International Journal of Molecular Sciences, vol. 21, no. 6, 2159. https://doi.org/10.3390/ijms21062159

APA

Nilov, D., Maluchenko, N., Kurgina, T., Pushkarev, S., Lys, A., Kutuzov, M., Gerasimova, N., Feofanov, A., Švedas, V., Lavrik, O., & Studitsky, V. M. (2020). Molecular mechanisms of PARP-1 inhibitor 7-methylguanine. International Journal of Molecular Sciences, 21(6), [2159]. https://doi.org/10.3390/ijms21062159

Vancouver

Nilov D, Maluchenko N, Kurgina T, Pushkarev S, Lys A, Kutuzov M et al. Molecular mechanisms of PARP-1 inhibitor 7-methylguanine. International Journal of Molecular Sciences. 2020 Mar;21(6):2159. doi: 10.3390/ijms21062159

Author

Nilov, Dmitry ; Maluchenko, Natalya ; Kurgina, Tatyana et al. / Molecular mechanisms of PARP-1 inhibitor 7-methylguanine. In: International Journal of Molecular Sciences. 2020 ; Vol. 21, No. 6.

BibTeX

@article{275e7b0fd1b440f3a5c15f4ab7dd872c,
title = "Molecular mechanisms of PARP-1 inhibitor 7-methylguanine",
abstract = "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 F{\"o}rster 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.",
keywords = "7-methylguanine, Docking, Fluorescence anisotropy, Inhibitor, Molecular dynamics, Nucleosome, Poly(ADP-ribose) polymerase 1, SpFRET microscopy, Trapping, poly(ADP-ribose) polymerase 1, POLY(ADP-RIBOSE) POLYMERASE, DOCKING, trapping, molecular dynamics, ACCURACY, docking, THERAPY, inhibitor, spFRET microscopy, fluorescence anisotropy, nucleosome, BINDING",
author = "Dmitry Nilov and Natalya Maluchenko and Tatyana Kurgina and Sergey Pushkarev and Alexandra Lys and Mikhail Kutuzov and Nadezhda Gerasimova and Alexey Feofanov and Vytas {\v S}vedas and Olga Lavrik and Studitsky, {Vasily M.}",
year = "2020",
month = mar,
doi = "10.3390/ijms21062159",
language = "English",
volume = "21",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

RIS

TY - JOUR

T1 - Molecular mechanisms of PARP-1 inhibitor 7-methylguanine

AU - Nilov, Dmitry

AU - Maluchenko, Natalya

AU - Kurgina, Tatyana

AU - Pushkarev, Sergey

AU - Lys, Alexandra

AU - Kutuzov, Mikhail

AU - Gerasimova, Nadezhda

AU - Feofanov, Alexey

AU - Švedas, Vytas

AU - Lavrik, Olga

AU - Studitsky, Vasily M.

PY - 2020/3

Y1 - 2020/3

N2 - 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.

AB - 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.

KW - 7-methylguanine

KW - Docking

KW - Fluorescence anisotropy

KW - Inhibitor

KW - Molecular dynamics

KW - Nucleosome

KW - Poly(ADP-ribose) polymerase 1

KW - SpFRET microscopy

KW - Trapping

KW - poly(ADP-ribose) polymerase 1

KW - POLY(ADP-RIBOSE) POLYMERASE

KW - DOCKING

KW - trapping

KW - molecular dynamics

KW - ACCURACY

KW - docking

KW - THERAPY

KW - inhibitor

KW - spFRET microscopy

KW - fluorescence anisotropy

KW - nucleosome

KW - BINDING

UR - http://www.scopus.com/inward/record.url?scp=85082310115&partnerID=8YFLogxK

U2 - 10.3390/ijms21062159

DO - 10.3390/ijms21062159

M3 - Article

C2 - 32245127

AN - SCOPUS:85082310115

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 6

M1 - 2159

ER -

ID: 23877110