A model for 3-methyladenine recognition by 3-methyladenine DNA glycosylase I (TAG) from Staphylococcus aureus.
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.
The BSRC, University of St Andrews, North Haugh, St Andrews KY16 9ST, Scotland.
Xiaofeng
X
Zhu
Xuan
X
Yan
Lester G
LG
Carter
Huanting
H
Liu
Shirley
S
Graham
Peter J
PJ
Coote
James
J
Naismith
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D045647:DNA Glycosylases / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D013211:Staphylococcus aureus / Q000201:enzymology*; D013379:Substrate Specificity
C025946:3-methyladenine; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D000225:Adenine