Сравнительный анализ активности полиморфных вариантов урацил-ДНК-гликолиаз человека человека SMUG1 и MBD4

Translated title of the contribution: Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4

I. V. Alekseeva, A. S. Bakman, D. A. Iakovlev, N. A. Kuznetsov, O. S. Fedorova

Research output: Contribution to journalArticlepeer-review

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.

Translated title of the contributionComparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4
Original languageRussian
Article number9
Pages (from-to)277-288
Number of pages12
JournalMolekuliarnaia biologiia
Volume55
Issue number2
DOIs
Publication statusPublished - 1 Mar 2021

Keywords

  • active site
  • catalysis
  • DNA repair
  • human uracil-DNA glycosylase
  • MBD4
  • polymorphic variant
  • SMUG1

OECD FOS+WOS

  • 3.02 CLINICAL MEDICINE

State classification of scientific and technological information

  • 76 MEDICINE AND HEALTH CARE

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