3buc

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X-ray structure of human ABH2 bound to dsDNA with Mn(II) and 2KG

Structural highlights

3buc is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.59Å
Ligands:AKG, MA7, MN, XL3
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ALKB2_HUMAN Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.[1] [2] [3] [4] [5]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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.

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[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5. Epub 2002 Dec 16. PMID:12486230 doi:10.1073/pnas.262589799
  2. ↑ Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003 Feb 20;421(6925):859-63. PMID:12594517 doi:10.1038/nature01363
  3. ↑ Lee DH, Jin SG, Cai S, Chen Y, Pfeifer GP, O'Connor TR. Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. J Biol Chem. 2005 Nov 25;280(47):39448-59. Epub 2005 Sep 20. PMID:16174769 doi:M509881200
  4. ↑ Ringvoll J, Moen MN, Nordstrand LM, Meira LB, Pang B, Bekkelund A, Dedon PC, Bjelland S, Samson LD, Falnes PO, Klungland A. AlkB homologue 2-mediated repair of ethenoadenine lesions in mammalian DNA. Cancer Res. 2008 Jun 1;68(11):4142-9. doi: 10.1158/0008-5472.CAN-08-0796. PMID:18519673 doi:http://dx.doi.org/10.1158/0008-5472.CAN-08-0796
  5. ↑ Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 doi:http://dx.doi.org/10.1038/nature06889
  6. ↑ Yang CG, Yi C, Duguid EM, Sullivan CT, Jian X, Rice PA, He C. Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA. Nature. 2008 Apr 24;452(7190):961-5. PMID:18432238 doi:http://dx.doi.org/10.1038/nature06889

Contents


PDB ID 3buc

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OCA

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