2YG8

Structure of an unusual 3-Methyladenine DNA Glycosylase II (Alka) from Deinococcus radiodurans

Summary for 2YG8

• Entry DOI: 10.2210/pdb2yg8/pdb
• Related: 2YG9
• Descriptor: DNA-3-methyladenine glycosidase II, putative, CHLORIDE ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: hydrolase, dna repair
• Biological source: Deinococcus radiodurans
• Total number of polymer chains: 2
• Total formula weight: 48367.27

Authors

Moe, E.,Hall, D.R.,Leiros, I.,Talstad, V.,Timmins, J.,McSweeney, S. (deposition date: 2011-04-11, release date: 2011-04-20, Last modification date: 2024-11-20)

Primary citation

Moe, E.,Hall, D.R.,Leiros, I.,Monsen, V.T.,Timmins, J.,McSweeney, S.
Structure-function studies of an unusual 3-methyladenine DNA glycosylase II (AlkA) from Deinococcus radiodurans.
Acta Crystallogr. D Biol. Crystallogr., 68:703-712, 2012

PubMed Abstract: 3-Methyladenine DNA glycosylase II (AlkA) is a DNA-repair enzyme that removes alkylated bases in DNA via the base-excision repair (BER) pathway. The enzyme belongs to the helix-hairpin-helix (HhH) superfamily of DNA glycosylases and possesses broad substrate specificity. In the genome of Deinococcus radiodurans, two genes encoding putative AlkA have been identified (Dr_2074 and Dr_2584). Dr_2074 is a homologue of human AlkA (MPG or AAG) and Dr_2584 is a homologue of bacterial AlkAs. Here, the three-dimensional structure of Dr_2584 (DrAlkA2) is presented and compared with the previously determined structure of Escherichia coli AlkA (EcAlkA). The results show that the enzyme consists of two helical-bundle domains separated by a wide DNA-binding cleft and contains an HhH motif. Overall, the protein fold is similar to the two helical-bundle domains of EcAlkA, while the third N-terminal mixed α/β domain observed in EcAlkA is absent. Substrate-specificity analyses show that DrAlkA2, like EcAlkA, is able to remove both 3-methyladenine (3meA) and 7-methylguanine (7meG) from DNA; however, the enzyme possesses no activity towards 1,N(6)-ethenoadenine (ℇA) and hypoxanthine (Hx). In addition, it shows activity towards the AlkB dioxygenase substrates 3-methylcytosine (3meC) and 1-methyladenine (1meA). Thus, the enzyme seems to preferentially repair methylated bases with weakened N-glycosidic bonds; this is an unusual specificity for a bacterial AlkA protein and is probably dictated by a combination of the wide DNA-binding cleft and a highly accessible specificity pocket.

PubMed: 22683793
DOI: 10.1107/S090744491200947X

Experimental method

X-RAY DIFFRACTION (2 Å)