AlkB demethylases flip out in different ways
| Autor: | Vivi Talstad, Ottar Sundheim, Geir Slupphaug, Hans E. Krokan, Cathrine Broberg Vågbø |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
DNA Repair
DNA damage Stereochemistry DNA repair Protein Conformation Molecular Sequence Data AlkB Molecular Conformation Biochemistry Dioxygenases Mixed Function Oxygenases chemistry.chemical_compound Protein structure Amino Acid Sequence Molecular Biology biology Sequence Homology Amino Acid AlkB Homolog 2 Alpha-Ketoglutarate-Dependent Dioxygenase Escherichia coli Proteins Cell Biology Base excision repair DNA DNA Methylation Cross-Linking Reagents DNA Repair Enzymes chemistry DNA glycosylase biology.protein Demethylase Nucleic Acid Conformation RNA DNA Damage |
| Zdroj: | DNA repair. 7(11) |
| ISSN: | 1568-7864 |
| Popis: | Aberrant methylations in DNA are repaired by base excision repair (BER) and direct repair by a methyltransferase or by an oxidative demethylase of the AlkB type. Yang et al. [Nature 452 (2008) 961-966] have now solved the crystal structure of AlkB and human AlkB homolog 2 (hABH2) in complex with DNA using an ingenious crosslinking strategy to stabilize the DNA-protein complex. AlkB proteins have similar catalytic domains, but different DNA recognition motifs. Whereas AlkB mainly makes contact with the damaged strand, hABH2 makes numerous contacts with both strands. hABH2 flips out the damaged base and fills the vacant space by a hydrophobic amino acid residue similar to DNA glycosylases, essentially without distorting the double helix structure. In contrast, AlkB squeezes together the bases flanking the flipped-out base to maintain the base stack. This unprecedented flipping mechanism and the differences between AlkB and hABH2 in contacting the DNA strands explain their preferences for single stranded- and double stranded DNA, respectively. |
| Databáze: | OpenAIRE |
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