3S5A

ABH2 cross-linked to undamaged dsDNA-2 with cofactors

Summary for 3S5A

• Entry DOI: 10.2210/pdb3s5a/pdb
• Related: 3BTY 3S57
• Descriptor: Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2, 5'-D(*CP*TP*GP*TP*CP*TP*CP*AP*CP*TP*GP*TP*CP*G)-3', 5'-D(*TP*CP*GP*AP*CP*AP*GP*TP*GP*AP*GP*AP*CP*A)-3', ... (8 entities in total)
• Functional Keywords: protein-dna complex, double helix, jelly-roll fold, dioxygenase, dna binding, cross-linking, oxidoreductase-dna complex, oxidoreductase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q6NS38
• Total number of polymer chains: 3
• Total formula weight: 32357.66

Authors

Yi, C.,Chen, B.,Qi, B.,Ramirez, B.,Zhang, W.,Jia, G.,Zhang, L.,Li, C.Q.,Dinner, A.R.,Yang, C.-G.,He, C. (deposition date: 2011-05-21, release date: 2012-06-06, Last modification date: 2024-03-20)

Primary citation

Yi, C.,Chen, B.,Qi, B.,Zhang, W.,Jia, G.,Zhang, L.,Li, C.J.,Dinner, A.R.,Yang, C.G.,He, C.
Duplex interrogation by a direct DNA repair protein in search of base damage
Nat.Struct.Mol.Biol., 19:671-676, 2012

PubMed Abstract: 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.

PubMed: 22659876
DOI: 10.1038/nsmb.2320

Experimental method

X-RAY DIFFRACTION (1.7 Å)