3BUC: X-Ray Structure Of Human Abh2 Bound To Dsdna With Mn(Ii) And 2kg

Citation:
Abstract
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.
PDB ID: 3BUCDownload
MMDB ID: 64014
PDB Deposition Date: 2008/1/2
Updated in MMDB: 2009/07
Experimental Method:
x-ray diffraction
Resolution: 2.59  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3BUC: trimeric; determined by author and by software (PISA)
Molecular Components in 3BUC
Label Count Molecule
Protein (1 molecule)
1
Alpha-ketoglutarate-dependent Dioxygenase Alkb Homolog 2(Gene symbol: ALKBH2)
Molecule annotation
Nucleotides(2 molecules)
1
DNA (5'-d(*dcp*dtp*dgp*dtp*dap*dtp*(ma7) P*dap*dcp*dtp*dgp*dcp*dg)-3')
Molecule annotation
1
DNA (5'- D(*dtp*dcp*dgp*dcp*dap*dgp*dtp*dtp*dap*dtp*dap*dcp*da)-3')
Molecule annotation
Chemicals (3 molecules)
1
1
2
1
3
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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