Interactions of the DNA Repair Enzyme Human Thymine DNA Glycosylase with Cognate and Noncognate DNA
Kanaan N, Imhof P (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 57
Pages Range: 5654-5665
Journal Issue: 39
DOI: 10.1021/acs.biochem.8b00409
Abstract
Glycosylases specifically recognize and flip their target base out of the DNA helix into the enzyme's active site. Our simulations show that a partially flipped state, already present in free DNA carrying a T:G mispair, becomes the more probable state compared to the closed state after binding of thymine DNA glycosylase (TDG). Paired thymine (T:A) or methyl-cytosine (mC:G) does not exhibit a partially flipped state in free or complexed DNA. Important enzyme-DNA interactions exhibit significant strength in the intrahelical and extrahelical TDG-DNA complexes. The computed binding free energy differences suggest these interactions account for the stabilization of the partially flipped state, thereby driving the T:G mispair toward base flip. In the fully flipped state, the cognate base thymine is significantly better accommodated in the enzyme's active site than noncognate bases are, suggesting the hydrolysis step as the last of several stages at which base recognition can be achieved.
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Germany (DE)How to cite
APA:
Kanaan, N., & Imhof, P. (2018). Interactions of the DNA Repair Enzyme Human Thymine DNA Glycosylase with Cognate and Noncognate DNA. Biochemistry, 57(39), 5654-5665. https://doi.org/10.1021/acs.biochem.8b00409
MLA:
Kanaan, Natalia, and Petra Imhof. "Interactions of the DNA Repair Enzyme Human Thymine DNA Glycosylase with Cognate and Noncognate DNA." Biochemistry 57.39 (2018): 5654-5665.
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