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Literature summary for 1.14.11.51 extracted from

  • Zhang, M.; Yang, S.; Nelakanti, R.; Zhao, W.; Liu, G.; Li, Z.; Liu, X.; Wu, T.; Xiao, A.; Li, H.
    Mammalian ALKBH1 serves as an N6-mA demethylase of unpairing DNA (2020), Cell Res., 30, 197-210 .
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
enzyme shows a stretch-out conformation of its Flip1 motif, explaining the observed preference of ALKBH1 for unpairing substrates, in which the flipped N6-mA is primed for catalysis. Structures of ALKBH1 bound to a 21-mer bulged DNA show the need of both flanking duplexes and a flipped base for recognition and catalysis Mus musculus

Protein Variants

Protein Variants Comment Organism
K158A mutation of basic residue of Flip1 region, abolishes N6-mA demethylation activity of ALKBH1 Mus musculus
R159A mutation of basic residue of Flip1 region, abolishes N6-mA demethylation activity of ALKBH1 Mus musculus
R160A mutation of basic residue of Flip1 region, abolishes N6-mA demethylation activity of ALKBH1 Mus musculus
R167A mutation of basic residue of Flip1 region, abolishes N6-mA demethylation activity of ALKBH1 Mus musculus
R169A mutation of basic residue of Flip1 region, abolishes N6-mA demethylation activity of ALKBH1 Mus musculus
S235D mutation disrupts N6-mA demethylation activity Mus musculus
S235E mutation disrupts N6-mA demethylation activity Mus musculus

Organism

Organism UniProt Comment Textmining
Mus musculus P0CB42
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information ALKBH1 prefers bubbled or bulged DNAs as substrate. The middle N6-mA in the 3-nt bulge is efficiently demethylated compared to that in the 3-nt bubble (97% vs. 18% demethylation fraction) and the 1st and 3rd N6-mAs are more resistant to demethylation. N6-mAs deposited in the flexible region of hairpin (DNA stem loop), D-loop and R-loop are efficiently demethylated as in bubble and bulge, while those in cruciform and replication fork are less demethylated. m6rA in RNA hairpin, RNA-RNA bubble and RNA-DNA hybrid bubble can also be demethylated by ALKBH1, as well as 5-methylcytosine at anticodon loop and 1-methyladenosine Mus musculus ?
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Synonyms

Synonyms Comment Organism
ALKBH1
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Mus musculus

General Information

General Information Comment Organism
metabolism N6-hydroxymethyladenine exists as an oxidized intermediate during N6-mA demethylation by ALKBH1 Mus musculus