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Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4. / Alekseeva, I.; Bakman, A. S.; Iakovlev, D. A. et al.

In: Molecular Biology, Vol. 55, No. 2, 03.2021, p. 241-251.

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

Harvard

Alekseeva, I, Bakman, AS, Iakovlev, DA, Kuznetsov, NA & Fedorova, OS 2021, 'Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4', Molecular Biology, vol. 55, no. 2, pp. 241-251. https://doi.org/10.1134/S0026893321020035

APA

Alekseeva, I., Bakman, A. S., Iakovlev, D. A., Kuznetsov, N. A., & Fedorova, O. S. (2021). Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4. Molecular Biology, 55(2), 241-251. https://doi.org/10.1134/S0026893321020035

Vancouver

Alekseeva I, Bakman AS, Iakovlev DA, Kuznetsov NA, Fedorova OS. Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4. Molecular Biology. 2021 Mar;55(2):241-251. doi: 10.1134/S0026893321020035

Author

Alekseeva, I. ; Bakman, A. S. ; Iakovlev, D. A. et al. / Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4. In: Molecular Biology. 2021 ; Vol. 55, No. 2. pp. 241-251.

BibTeX

@article{d847b71dbac348bca7ec8d6e8285550b,
title = "Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4",
abstract = "The human N-glycosylases SMUG1 and MBD4 catalyze the removal of uracil residues from DNA resulting from cytosine deamination or replication errors. For polymorphic variants of SMUG1 (G90C, P240H, N244S, N248Y) and the MBD4(cat) catalytic domain (S470L, G507S, R512W, H557D), the structures of enzyme-substrate complexes were obtained by molecular dynamic simulation. It was experimentally found that the SNP variants of SMUG1, N244S and N248Y, had increased catalytic activity compared to the wild-type enzyme, probably due to the acceleration of the dissociation of the enzyme-product complex and an increase in the enzyme turnover rate. All other SNP variants of SMUG1 (G90C, P240H) and MBD4(cat), in which amino acid substitutions disrupted the substrate binding region and/or active site, had significantly lower catalytic activity than the wild-type enzymes.",
keywords = "DNA repair, human uracil-DNA glycosylase, MBD4, SMUG1, polymorphic variant, active site, catalysis, BASE EXCISION-REPAIR, DAMAGE-RECOGNITION, STRUCTURAL BASIS, PROTEINS, DOMAIN, GENES, SPECIFICITY, MECHANISM, DEMETHYLATION, DEAMINATION",
author = "I. Alekseeva and Bakman, {A. S.} and Iakovlev, {D. A.} and Kuznetsov, {N. A.} and Fedorova, {O. S.}",
note = "This work was supported by grant no. 16-14-10038 from the Russian Science Foundation and partial support from budgetary funding (no. AAAA-A17-117020210022-4) to ensure routine maintenance of the equipment.",
year = "2021",
month = mar,
doi = "10.1134/S0026893321020035",
language = "English",
volume = "55",
pages = "241--251",
journal = "Molecular Biology",
issn = "0026-8933",
publisher = "Maik Nauka-Interperiodica Publishing",
number = "2",

}

RIS

TY - JOUR

T1 - Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4

AU - Alekseeva, I.

AU - Bakman, A. S.

AU - Iakovlev, D. A.

AU - Kuznetsov, N. A.

AU - Fedorova, O. S.

N1 - This work was supported by grant no. 16-14-10038 from the Russian Science Foundation and partial support from budgetary funding (no. AAAA-A17-117020210022-4) to ensure routine maintenance of the equipment.

PY - 2021/3

Y1 - 2021/3

N2 - The human N-glycosylases SMUG1 and MBD4 catalyze the removal of uracil residues from DNA resulting from cytosine deamination or replication errors. For polymorphic variants of SMUG1 (G90C, P240H, N244S, N248Y) and the MBD4(cat) catalytic domain (S470L, G507S, R512W, H557D), the structures of enzyme-substrate complexes were obtained by molecular dynamic simulation. It was experimentally found that the SNP variants of SMUG1, N244S and N248Y, had increased catalytic activity compared to the wild-type enzyme, probably due to the acceleration of the dissociation of the enzyme-product complex and an increase in the enzyme turnover rate. All other SNP variants of SMUG1 (G90C, P240H) and MBD4(cat), in which amino acid substitutions disrupted the substrate binding region and/or active site, had significantly lower catalytic activity than the wild-type enzymes.

AB - The human N-glycosylases SMUG1 and MBD4 catalyze the removal of uracil residues from DNA resulting from cytosine deamination or replication errors. For polymorphic variants of SMUG1 (G90C, P240H, N244S, N248Y) and the MBD4(cat) catalytic domain (S470L, G507S, R512W, H557D), the structures of enzyme-substrate complexes were obtained by molecular dynamic simulation. It was experimentally found that the SNP variants of SMUG1, N244S and N248Y, had increased catalytic activity compared to the wild-type enzyme, probably due to the acceleration of the dissociation of the enzyme-product complex and an increase in the enzyme turnover rate. All other SNP variants of SMUG1 (G90C, P240H) and MBD4(cat), in which amino acid substitutions disrupted the substrate binding region and/or active site, had significantly lower catalytic activity than the wild-type enzymes.

KW - DNA repair

KW - human uracil-DNA glycosylase

KW - MBD4

KW - SMUG1

KW - polymorphic variant

KW - active site

KW - catalysis

KW - BASE EXCISION-REPAIR

KW - DAMAGE-RECOGNITION

KW - STRUCTURAL BASIS

KW - PROTEINS

KW - DOMAIN

KW - GENES

KW - SPECIFICITY

KW - MECHANISM

KW - DEMETHYLATION

KW - DEAMINATION

U2 - 10.1134/S0026893321020035

DO - 10.1134/S0026893321020035

M3 - Article

VL - 55

SP - 241

EP - 251

JO - Molecular Biology

JF - Molecular Biology

SN - 0026-8933

IS - 2

ER -

ID: 34690198