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Active and alkylated human AGT structures: a novel zinc site, inhibitor and extrahelical base binding
- D. Daniels, C. Mol, A. Arvai, S. Kanugula, A. Pegg, J. Tainer
- Chemistry, BiologyThe EMBO journal
- 3 April 2000
These results support damaged nucleotide flipping facilitated by an arginine finger within the HTH motif to stabilize the extrahelical O6‐alkylguanine without the protein conformational change originally proposed from the empty Ada structure.
Inactivation and degradation of O(6)-alkylguanine-DNA alkyltransferase after reaction with nitric oxide.
Exposure to NO causes an irreversible loss of DNA repair capacity for alkylation adducts, which may contribute toward the potential development of tumors in cells upon chronic exposure to NO because of inflammation or infection.
The repair of the tobacco specific nitrosamine derived adduct O6-[4-Oxo-4-(3-pyridyl)butyl]guanine by O6-alkylguanine-DNA alkyltransferase variants.
- R. S. Mijal, N. Thomson, L. Peterson
- Biology, ChemistryChemical research in toxicology
- 12 February 2004
Inefficient repair of O6-pobG by bacterial AGT explains the high mutagenic activity of this adduct in bacterial systems and differences observed in the repair by mammalian proteins may translate into differences in sensitivity to themutagenic and carcinogenic effects of NNK or other pyridyloxobutylating nitrosamines.
Isolation of human O6-alkylguanine-DNA alkyltransferase mutants highly resistant to inactivation by O6-benzylguanine.
Results indicate that this screening method can be used to evaluate BG resistance of single or multiple changes throughout the AGT sequence; and replacement of proline-140 with lysine is the most effective point mutation at this site causing BG resistance and is more than 200 times more effective than replacement with alanine.
8-Substituted O6-benzylguanine, substituted 6(4)-(benzyloxy)pyrimidine, and related derivatives as inactivators of human O6-alkylguanine-DNA alkyltransferase.
- M. Chae, K. Swenn, S. Kanugula, M. Dolan, A. Pegg, R. Moschel
- Chemistry, BiologyJournal of medicinal chemistry
- 20 January 1995
Provided these types of purines and pyrimidines do not exhibit undesirable toxicity, they may be superior to O6-benzylguanine as chemotherapeutic adjuvants for enhancing the effectiveness of antitumor drugs for which the mechanism of action involves modification of the O 6-position of DNA guanine residues.
Alkylated DNA damage flipping bridges base and nucleotide excision repair
The analysis of lesion-binding site conservation identifies new ATLs in sea anemone and ancestral archaea, indicating that ATL interactions are ancestral to present-day repair pathways in all domains of life.
Alteration of arginine-128 to alanine abolishes the ability of human O6-alkylguanine-DNA alkyltransferase to repair methylated DNA but has no effect on its reaction with O6-benzylguanine.
Results suggest that the residues arginine-128 and tyrosine-114 are involved in the DNA binding properties of the AGT.
Characterization of a Mutagenic DNA Adduct Formed from 1,2-Dibromoethane by O6-Alkylguanine-DNA Alkyltransferase*
Chemical and biological evidence supports the existence of at least two alkyltransferase-dependent pathways for 1,2-dibromoethane-induced mutagenicity, one involving Gua N7-alkylation by alKYl transferase-S-CH2CH2Br and depurination, plus another as yet uncharacterized system(s).
A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O6-alkylguanine-DNA alkyltransferase and endonuclease V activities.
- S. Kanugula, G. Pauly, R. Moschel, A. Pegg
- Biology, ChemistryProceedings of the National Academy of Sciences…
- 8 March 2005
The results demonstrate the physiological occurrence of two completely different but functional DNA repair activities in a single polypeptide chain.
Investigation of the role of tyrosine-114 in the activity of human O6-alkylguanine-DNA alkyltranferase.
The results show that when large amounts of AGT are produced in the cell, substantial decreases in the efficiency with which AGT can repair methylated DNA do not prevent the ability to protect E. coli from toxic alkylating agents.