1KEA

STRUCTURE OF A THERMOSTABLE THYMINE-DNA GLYCOSYLASE

Summary for 1KEA

• Entry DOI: 10.2210/pdb1kea/pdb
• Descriptor: Possible G-T mismatches repair enzyme, ZINC ION, ACETATE ION, ... (6 entities in total)
• Functional Keywords: dna repair, dna glycosylase, dna mismatch, methylation, base twisting, hydrolase
• Biological source: Methanothermobacter thermautotrophicus
• Total number of polymer chains: 1
• Total formula weight: 26167.94

Authors

Mol, C.D.,Arvai, A.S.,Begley, T.J.,Cunningham, R.P.,Tainer, J.A. (deposition date: 2001-11-14, release date: 2002-01-23, Last modification date: 2024-02-07)

Primary citation

Mol, C.D.,Arvai, A.S.,Begley, T.J.,Cunningham, R.P.,Tainer, J.A.
Structure and activity of a thermostable thymine-DNA glycosylase: evidence for base twisting to remove mismatched normal DNA bases.
J.Mol.Biol., 315:373-384, 2002

PubMed Abstract: The repair of T:G mismatches in DNA is key for maintaining bacterial restriction/modification systems and gene silencing in higher eukaryotes. T:G mismatch repair can be initiated by a specific mismatch glycosylase (MIG) that is homologous to the helix-hairpin-helix (HhH) DNA repair enzymes. Here, we present a 2.0 A resolution crystal structure and complementary mutagenesis results for this thermophilic HhH MIG enzyme. The results suggest that MIG distorts the target thymine nucleotide by twisting the thymine base approximately 90 degrees away from its normal anti position within DNA. We propose that functionally significant differences exist in DNA repair enzyme extrahelical nucleotide binding and catalysis that are characteristic of whether the target base is damaged or is a normal base within a mispair. These results explain why pure HhH DNA glycosylases and combined glycosylase/AP lyases cannot be interconverted by simply altering their functional group chemistry, and how broad-specificity DNA glycosylase enzymes may weaken the glycosylic linkage to allow a variety of damaged DNA bases to be excised.

PubMed: 11786018
DOI: 10.1006/jmbi.2001.5264

Experimental method

X-RAY DIFFRACTION (2 Å)