RSS

PDB:1RRQ

Protein Name

MutY adenine DNA glycosylase/DNA lesion in A*oxoG pair complex

Species

Bacillus stearothermophilus (bacteria)

Biological Context

Aerobic organisms generate energy from ATP with the help of oxygen. Their genes, in particular guanine bases, are therefore oxidized easily. Oxidized guanine, 8-oxoguanine (oxoG) is a genotoxic product. Replicative DNA polymerases misread oxoG and insert adenine instead of cytosine opposite to the oxidized base of oxoG. Both bases of the adenine-oxoG mismatch pair are mutagenic DNA lesions and considered one of the causes for cancers and aging. Therefore they have to undergo DNA-repair such as the replacement of the mismatch pair with a cytosine-guanine pair. The DNA-repair machinery involves the following steps; an adenine base of the adenine-oxoG mismatch pair is removed through the catalytic action of adenine DNA glycosylases, generating an abasic site. Then repair polymerases replace a cytosine with the abasic site. The resulting cytosine-oxoG pair undergoes removal of oxoG by 8-oxoguanine DNA glycosylases, and a guanine is inserted through the catalysis of repair polymerases. Thus a biologically functional C-G pair is restored.

Structure Description

1rrq1rrq_x1rrq_y

The structure of a complex of adenine DNA glycosylase, MutY, with double stranded DNA has been determined. MutY finds adenine-oxoG mismatch pairs and removes the adenine base of this pair. This enzyme has a catalytic domain constructed of two modules, a [4Fe-4S] cluster and a six-helix barrel module, and provides a deep pocket for the substrate, formed at the junction of the two modules. The C-terminal domain of MutY contacts the oxoG-side strand, but interacts with the MutY catalytic domain as well. This interdomain contact allows MutY to encircle the DNA duplex. The adenine base of adenine-oxoG protrudes from the DNA helix and therefore readily fits into the pocket in the MutY catalytic domain. Subsequently the adenine base is removed. In this way MutY recognizes adenine-oxoG lesions and removes the adenine base.

Protein Data Bank (PDB)

References

Source

Fromme, J.C. Banerjee, A. Huang, S.J. Verdine, G.L.; "Structural basis for removal of adenine mispaired with 8-oxoguanine by MutY adenine DNA glycosylase"; Nature; (2004) 427:652-656 PubMed:14961129.

Others

author: Yuko Tsuchiya


Japanese version:PDB:1RRQ