3bu0: Difference between revisions
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'''crystal structure of human ABH2 cross-linked to dsDNA with cofactors''' | '''crystal structure of human ABH2 cross-linked to dsDNA with cofactors''' | ||
==Overview== | |||
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein. | |||
==About this Structure== | ==About this Structure== | ||
3BU0 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU0 OCA]. | 3BU0 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BU0 OCA]. | ||
==Reference== | |||
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA., Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C, Nature. 2008 Apr 24;452(7190):961-5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18432238 18432238] | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: Oxidoreductase/dna complex]] | [[Category: Oxidoreductase/dna complex]] | ||
[[Category: Protein/dna interaction]] | [[Category: Protein/dna interaction]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:57:31 2008'' | ||
Revision as of 10:57, 11 June 2008
crystal structure of human ABH2 cross-linked to dsDNA with cofactors
OverviewOverview
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.
About this StructureAbout this Structure
3BU0 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA., Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C, Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 Page seeded by OCA on Wed Jun 11 10:57:31 2008