Alpha-ketoglutarate-dependent dioxygenase AlkB (P05050)

Identification
Name:Alpha-ketoglutarate-dependent dioxygenase AlkB
Synonyms:
  • Alkylated DNA repair protein AlkB
  • DNA oxidative demethylase AlkB
Gene Name:alkB
Enzyme Class:
Biological Properties
General Function:Not Available
Specific Function:Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents). Dioxygenase that repairs alkylated DNA and RNA containing 3-methylcytosine or 1-methyladenine by oxidative demethylation. Has highest activity towards 3-methylcytosine. Has lower activity towards alkylated DNA containing ethenoadenine, and no detectable activity towards 1-methylguanine or 3-methylthymine. Accepts double-stranded and single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron. Provides extensive resistance to alkylating agents such as MMS and DMS (SN2 agents), but not to MMNG and MNU (SN1 agents).
Cellular Location:Not Available
SMPDB Pathways:
  • Collection of Reactions without pathways PW001891
KEGG Pathways:Not Available
Complex Reactions:
1.0DNA-base-CH(3)+1.0Thumb+1.0Thumb → 1.0DNA-base+1.0Thumb+1.0Thumb+1.0Thumb
1.0DNA-base-CH(3) + 1.0Oxoglutaric acid + 1.0Oxygen → 1.0DNA-base + 1.0Formaldehyde + 1.0Succinic acid + 1.0Carbon dioxide
ReactionCard
Metabolites:
ECMDB IDNameView
ECMDB202201-EthyladenineMetaboCard
ECMDB00990AcetaldehydeMetaboCard
ECMDB00034AdenineMetaboCard
ECMDB04030Carbon dioxideMetaboCard
ECMDB01426FormaldehydeMetaboCard
ECMDB20590N1-MethyladenineMetaboCard
ECMDB20591N3-MethylcytosineMetaboCard
ECMDB04123Oxoglutaric acidMetaboCard
ECMDB04124OxygenMetaboCard
ECMDB00254Succinic acidMetaboCard
GO Classification:Not Available
Gene Properties
Blattner:b2212
Gene OrientationNot Available
Centisome Percentage:Not Available
Left Sequence EndNot Available
Right Sequence EndNot Available
Gene Sequence:
>ENA|AAC75272|AAC75272.1 Escherichia coli str. K-12 substr. MG1655 oxidative demethylase of N1-methyladenine or N3-methylcytosine DNA lesions
ATGTTGGATCTGTTTGCCGATGCTGAACCGTGGCAAGAGCCACTGGCGGCTGGTGCGGTA
ATTTTACGGCGTTTTGCTTTTAACGCTGCGGAGCAACTGATCCGCGATATTAATGACGTT
GCCAGCCAGTCGCCGTTTCGCCAGATGGTCACCCCCGGGGGATATACCATGTCGGTGGCG
ATGACCAACTGTGGGCATCTGGGCTGGACGACCCATCGGCAAGGTTATCTCTATTCGCCC
ATTGATCCGCAAACAAATAAACCGTGGCCCGCCATGCCACAGAGTTTTCATAATTTATGT
CAACGTGCGGCTACGGCGGCGGGCTATCCAGATTTCCAGCCAGATGCTTGTCTTATCAAC
CGCTACGCTCCTGGCGCGAAACTGTCGCTGCATCAGGATAAAGACGAACCGGATCTGCGC
GCGCCAATTGTTTCTGTTTCTCTGGGCTTACCCGCGATTTTTCAATTTGGCGGCCTGAAA
CGAAATGATCCGCTCAAACGTTTGTTGTTGGAACATGGCGATGTGGTGGTATGGGGCGGT
GAATCGCGGCTGTTTTATCACGGTATTCAACCGTTGAAAGCGGGGTTTCATCCACTCACC
ATCGACTGCCGCTACAACCTGACATTCCGTCAGGCAGGTAAAAAAGAATAA
Protein Properties
Pfam Domain Function:Not Available
Protein Residues:Not Available
Protein Molecular Weight:Not Available
Protein Theoretical pI:Not Available
Signaling Regions:Not Available
Transmembrane Regions:Not Available
Protein Sequence:
>sp|P05050|ALKB_ECOLI Alpha-ketoglutarate-dependent dioxygenase AlkB OS=Escherichia coli (strain K12) GN=alkB PE=1 SV=1
MLDLFADAEPWQEPLAAGAVILRRFAFNAAEQLIRDINDVASQSPFRQMVTPGGYTMSVA
MTNCGHLGWTTHRQGYLYSPIDPQTNKPWPAMPQSFHNLCQRAATAAGYPDFQPDACLIN
RYAPGAKLSLHQDKDEPDLRAPIVSVSLGLPAIFQFGGLKRNDPLKRLLLEHGDVVVWGG
ESRLFYHGIQPLKAGFHPLTIDCRYNLTFRQAGKKE
References
External Links:
ResourceLink
Uniprot ID:P05050
ColiBase:b2212
Kegg Gene:b2212
BacMap:16130149
General Reference:
  • Aas, P. A., Otterlei, M., Falnes, P. O., Vagbo, C. B., Skorpen, F., Akbari, M., Sundheim, O., Bjoras, M., Slupphaug, G., Seeberg, E., Krokan, H. E. (2003). "Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA." Nature 421:859-863. Pubmed: 12594517
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Chen, B. J., Carroll, P., Samson, L. (1994). "The Escherichia coli AlkB protein protects human cells against alkylation-induced toxicity." J Bacteriol 176:6255-6261. Pubmed: 7928996
  • Demple, B., Sedgwick, B., Robins, P., Totty, N., Waterfield, M. D., Lindahl, T. (1985). "Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis." Proc Natl Acad Sci U S A 82:2688-2692. Pubmed: 3887409
  • Falnes, P. O., Johansen, R. F., Seeberg, E. (2002). "AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli." Nature 419:178-182. Pubmed: 12226668
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • Holland, P. J., Hollis, T. (2010). "Structural and mutational analysis of Escherichia coli AlkB provides insight into substrate specificity and DNA damage searching." PLoS One 5:e8680. Pubmed: 20084272
  • Itoh, T., Aiba, H., Baba, T., Hayashi, K., Inada, T., Isono, K., Kasai, H., Kimura, S., Kitakawa, M., Kitagawa, M., Makino, K., Miki, T., Mizobuchi, K., Mori, H., Mori, T., Motomura, K., Nakade, S., Nakamura, Y., Nashimoto, H., Nishio, Y., Oshima, T., Saito, N., Sampei, G., Seki, Y., Horiuchi, T., et, a. l. .. (1996). "A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map." DNA Res 3:379-392. Pubmed: 9097040
  • Kondo, H., Nakabeppu, Y., Kataoka, H., Kuhara, S., Kawabata, S., Sekiguchi, M. (1986). "Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA." J Biol Chem 261:15772-15777. Pubmed: 3536913
  • Yang, C. G., Yi, C., Duguid, E. M., Sullivan, C. T., Jian, X., Rice, P. A., He, C. (2008). "Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA." Nature 452:961-965. Pubmed: 18432238
  • Yi, C., Jia, G., Hou, G., Dai, Q., Zhang, W., Zheng, G., Jian, X., Yang, C. G., Cui, Q., He, C. (2010). "Iron-catalysed oxidation intermediates captured in a DNA repair dioxygenase." Nature 468:330-333. Pubmed: 21068844
  • Yu, B., Edstrom, W. C., Benach, J., Hamuro, Y., Weber, P. C., Gibney, B. R., Hunt, J. F. (2006). "Crystal structures of catalytic complexes of the oxidative DNA/RNA repair enzyme AlkB." Nature 439:879-884. Pubmed: 16482161
  • Yu, B., Hunt, J. F. (2009). "Enzymological and structural studies of the mechanism of promiscuous substrate recognition by the oxidative DNA repair enzyme AlkB." Proc Natl Acad Sci U S A 106:14315-14320. Pubmed: 19706517