Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
08 03 2023
Historique:
received: 21 12 2022
accepted: 27 02 2023
entrez: 8 3 2023
pubmed: 9 3 2023
medline: 11 3 2023
Statut: epublish

Résumé

Uracil DNA-glycosylase (UNG) is a DNA repair enzyme that removes the highly mutagenic uracil lesion from DNA using a base flipping mechanism. Although this enzyme has evolved to remove uracil from diverse sequence contexts, UNG excision efficiency depends on DNA sequence. To provide the molecular basis for rationalizing UNG substrate preferences, we used time-resolved fluorescence spectroscopy, NMR imino proton exchange measurements, and molecular dynamics simulations to measure UNG specificity constants (k

Identifiants

pubmed: 36890276
doi: 10.1038/s41598-023-30620-0
pii: 10.1038/s41598-023-30620-0
pmc: PMC9995336
doi:

Substances chimiques

DNA 9007-49-2
Uracil 56HH86ZVCT
Uracil-DNA Glycosidase EC 3.2.2.-

Types de publication

Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3915

Subventions

Organisme : NIH HHS
ID : R35GM141933
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

Paul B Orndorff (PB)

Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA.

Souvik Poddar (S)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA.
The Biodesign Institute Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, 85287, USA.

Aerial M Owens (AM)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA.
The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA.

Nikita Kumari (N)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA.
The Biodesign Institute Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, 85287, USA.

Bryan T Ugaz (BT)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA.
The Biodesign Institute Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, 85287, USA.

Samrat Amin (S)

Magnetic Resonance Research Center, Arizona State University, Tempe, AZ, 85287, USA.

Wade D Van Horn (WD)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA. wade.van.horn@asu.edu.
The Biodesign Institute Virginia G. Piper Center for Personalized Diagnostics, Arizona State University, Tempe, AZ, 85287, USA. wade.van.horn@asu.edu.

Arjan van der Vaart (A)

Department of Chemistry, University of South Florida, Tampa, FL, 33620, USA. avandervaart@usf.edu.

Marcia Levitus (M)

School of Molecular Sciences, Arizona State University, Tempe, AZ, 85287, USA. marcia.levitus@asu.edu.
The Biodesign Institute Center for Single Molecule Biophysics, Arizona State University, Tempe, AZ, 85287, USA. marcia.levitus@asu.edu.

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Classifications MeSH