Open AccessA model for 3‐methyladenine recognition by 3‐methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus
Author(s) -
Zhu Xiaofeng,
Yan Xuan,
Carter Lester G.,
Liu Huanting,
Graham Shirley,
Coote Peter J.,
Naismith James
Publication year - 2012
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309112016363
Subject(s) - dna glycosylase , isothermal titration calorimetry , chemistry , dna , biochemistry , tautomer , protonation , staphylococcus aureus , enzyme , stereochemistry , biophysics , dna repair , biology , genetics , organic chemistry , bacteria , ion
The removal of chemically damaged DNA bases such as 3‐methyladenine (3‐MeA) is an essential process in all living organisms and is catalyzed by the enzyme 3‐MeA DNA glycosylase I. A key question is how the enzyme selectively recognizes the alkylated 3‐MeA over the much more abundant adenine. The crystal structures of native and Y16F‐mutant 3‐MeA DNA glycosylase I from Staphylococcus aureus in complex with 3‐MeA are reported to 1.8 and 2.2 Å resolution, respectively. Isothermal titration calorimetry shows that protonation of 3‐MeA decreases its binding affinity, confirming previous fluorescence studies that show that charge–charge recognition is not critical for the selection of 3‐MeA over adenine. It is hypothesized that the hydrogen‐bonding pattern of Glu38 and Tyr16 of 3‐MeA DNA glycosylase I with a particular tautomer unique to 3‐MeA contributes to recognition and selection.
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