3RZL: Duplex Interrogation By A Direct Dna Repair Protein In The Search Of Damage

ALKBH2 is a direct DNA repair dioxygenase guarding the mammalian genome against N(1)-methyladenine, N(3)-methylcytosine and 1,N(6)-ethenoadenine damage. A prerequisite for repair is to identify these lesions in the genome. Here we present crystal structures of human ALKBH2 bound to different duplex DNAs. Together with computational and biochemical analyses, our results suggest that DNA interrogation by ALKBH2 has two previously unknown features: (i) ALKBH2 probes base-pair stability and detects base pairs with reduced stability, and (ii) ALKBH2 does not have nor need a damage-checking site, which is critical for preventing spurious base cleavage for several glycosylases. The demethylation mechanism of ALKBH2 insures that only cognate lesions are oxidized and reversed to normal bases, and that a flipped, non-substrate base remains intact in the active site. Overall, the combination of duplex interrogation and oxidation chemistry allows ALKBH2 to detect and process diverse lesions efficiently and correctly.
PDB ID: 3RZLDownload
MMDB ID: 100241
PDB Deposition Date: 2011/5/11
Updated in MMDB: 2013/07
Experimental Method:
x-ray diffraction
Resolution: 2.6  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 3RZL: trimeric; determined by author and by software (PISA)
Molecular Components in 3RZL
Label Count Molecule
Protein (1 molecule)
Alpha-ketoglutarate-dependent Dioxygenase Alkb Homolog 2(Gene symbol: ALKBH2)
Molecule annotation
Nucleotides(2 molecules)
Molecule annotation
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB