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Title:
The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin | Science China Chemistry
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Mammalian AlkB homologue 2 (ALKBH2) is the primary housekeeping DNA demethylase, effectively repairing endogenously formed methylated lesions in double-stranded DNA. Our previous studies demonstrated that a hydrophobic β-hairpin motif of ALKBH2 could play crucial roles in base-pair stability interrogation and damaged base flipping. Using chemical cross-linking strategy, we obtained two crystal structures of human ALKBH2 mutant bound to duplex DNA. The structural analysis suggests that the β-hairpin motif is flexible in conformation and is likely to slide along the DNA duplex in local regions to search for damaged base. This study provides a new mechanistic insight into DNA damage detection by ALKBH2.
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article, dna, google, scholar, cas, repair, alkbh, damage, yang, biol, search, chen, human, access, protein, crystallogr, privacy, cookies, content, china, βhairpin, nature, verdine, data, publish, science, structures, chemical, gan, alkb, demethylase, motif, sedgwick, rev, mol, alkylation, chem, aas, krokan, sci, information, log, journal, research, complex, dsdna, reveal, jianhua, caiguang, repairing,
Topics {✒️}
chemical cross-linking strategy hydrophobic β-hairpin motif month download article/chapter repairing dna-methylation damage alkbh2 mutants cross-linked double-stranded dna substrates β-hairpin motif dna damage detection base-pair stability interrogation dna alkylation damage double-stranded dna damaged dna bases primary oxidative demethylase protein-dna complexes dna glycosylase enzymes full article pdf privacy choices/manage cookies β-hairpin dna repair dna glycosylase searching human alkb-homologues 2 n6-ma demethylase mammalian alkbh1 serves related subjects base damage damaged base flipping single-stranded annu rev biochem european economic area previous studies demonstrated play crucial roles pediatric brain tumors hiv-1 reverse transcriptase model-building tools nucleic acids res human glioblastoma cells check access instant access article chen conditions privacy policy structural analysis suggests caiguang yang acc chem res accepting optional cookies chemical biology alkb homologue regulating muc1 expression authors correspondence main content log conformation
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headline:The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin
description:Mammalian AlkB homologue 2 (ALKBH2) is the primary housekeeping DNA demethylase, effectively repairing endogenously formed methylated lesions in double-stranded DNA. Our previous studies demonstrated that a hydrophobic β-hairpin motif of ALKBH2 could play crucial roles in base-pair stability interrogation and damaged base flipping. Using chemical cross-linking strategy, we obtained two crystal structures of human ALKBH2 mutant bound to duplex DNA. The structural analysis suggests that the β-hairpin motif is flexible in conformation and is likely to slide along the DNA duplex in local regions to search for damaged base. This study provides a new mechanistic insight into DNA damage detection by ALKBH2.
datePublished:2013-12-17T00:00:00Z
dateModified:2013-12-17T00:00:00Z
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chemical cross-linking
β-hairpin motif
damage detection
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headline:The complex structures of ALKBH2 mutants cross-linked to dsDNA reveal the conformational swing of β-hairpin
description:Mammalian AlkB homologue 2 (ALKBH2) is the primary housekeeping DNA demethylase, effectively repairing endogenously formed methylated lesions in double-stranded DNA. Our previous studies demonstrated that a hydrophobic β-hairpin motif of ALKBH2 could play crucial roles in base-pair stability interrogation and damaged base flipping. Using chemical cross-linking strategy, we obtained two crystal structures of human ALKBH2 mutant bound to duplex DNA. The structural analysis suggests that the β-hairpin motif is flexible in conformation and is likely to slide along the DNA duplex in local regions to search for damaged base. This study provides a new mechanistic insight into DNA damage detection by ALKBH2.
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