This domain is found at the N terminus of bacterial AlkA . AlkA (3-methyladenine-DNA glycosylase II) is a base excision repair glycosylase from Escherichia coli. It removes a variety of alkylated bases from DNA, primarily by removing alkylation damage from duplex and single stranded DNA. AlkA flips a 1-azaribose abasic nucleotide out of DNA. This produces a 66 degrees bend in the DNA and a marked widening of the minor groove (PUBMED:10675345).
AlkA (DNA-3-methyladenine glycosylase II) is a base excision repair glycosylase from Escherichia coli. It removes a variety of alkylated bases from DNA, primarily by removing alkylation damage from duplex and single stranded DNA. AlkA is similar in fold and active site location to the bifunctional glycosylase/lyase endonuclease III. This suggests that the two may use similar mechanisms for base excision [ (PUBMED:8706136) ]. The structural analysis of the AlkA and AlkA-hypoxanthine structures indicate that free hypoxanthine binding in the active site may inhibit glycosylase activity [ (PUBMED:12009927) ].
The AlkA protein consists of three domains: an N-terminal mixed alpha-beta structure, a central seven-helix bundle, and a C-terminal domain of four a helices [ (PUBMED:8706136) ]. This entry represents the N-terminal domain.
Family alignment:
There are 6580 AlkA_N domains in 6579 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing AlkA_N domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with AlkA_N domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing AlkA_N domain in the selected taxonomic class.
DNA bending and a flip-out mechanism for base excision by thehelix-hairpin-helix DNA glycosylase, Escherichia coli AlkA.
EMBO J. 2000; 19: 758-66
Display abstract
The Escherichia coli AlkA protein is a base excision repair glycosylasethat removes a variety of alkylated bases from DNA. The 2.5 A crystalstructure of AlkA complexed to DNA shows a large distortion in the boundDNA. The enzyme flips a 1-azaribose abasic nucleotide out of DNA andinduces a 66 degrees bend in the DNA with a marked widening of the minorgroove. The position of the 1-azaribose in the enzyme active site suggestsan S(N)1-type mechanism for the glycosylase reaction, in which theessential catalytic Asp238 provides direct assistance for base removal.Catalytic selectivity might result from the enhanced stacking ofpositively charged, alkylated bases against the aromatic side chain ofTrp272 in conjunction with the relative ease of cleaving the weakenedglycosylic bond of these modified nucleotides. The structure of theAlkA-DNA complex offers the first glimpse of a helix-hairpin-helix (HhH)glycosylase complexed to DNA. Modeling studies suggest that other HhHglycosylases can bind to DNA in a similar manner.
Structural basis for the excision repair of alkylation-damaged DNA.
Cell. 1996; 86: 321-9
Display abstract
Base-excision DNA repair proteins that target alkylation damage act on a variety of seemingly dissimilar adducts, yet fail to recognize other closely related lesions. The 1.8 A crystal structure of the monofunctional DNA glycosylase AlkA (E. coli 3-methyladenine-DNA glycosylase II) reveals a large hydrophobic cleft unusually rich in aromatic residues. An Asp residue projecting into this cleft is essential for catalysis, and it governs binding specificity for mechanism-based inhibitors. We propose that AlkA recognizes electron-deficient methylated bases through pi-donor/acceptor interactions involving the electron-rich aromatic cleft. Remarkably, AlkA is similar in fold and active site location to the bifunctional glycosylase/lyase endonuclease III, suggesting the two may employ fundamentally related mechanisms for base excision.
