1oe6: Difference between revisions

Cytosine deamination is a major promutagenic process, generating G:U, mismatches that can cause transition mutations if not repaired. Uracil is, also introduced into DNA via nonmutagenic incorporation of dUTP during, replication. In bacteria, uracil is excised by uracil-DNA glycosylases, (UDG) related to E. coli UNG, and UNG homologs are found in mammals and, viruses. Ung knockout mice display no increase in mutation frequency due, to a second UDG activity, SMUG1, which is specialized for antimutational, uracil excision in mammalian cells. Remarkably, SMUG1 also excises the, oxidation-damage product 5-hydroxymethyluracil (HmU), but like UNG is, inactive against thymine (5-methyluracil), a chemical substructure of HmU., We have solved the crystal structure of SMUG1 complexed with DNA and, base-excision products. This structure indicates a more invasive, interaction with dsDNA than observed with other UDGs and reveals an, elegant water displacement/replacement mechanism that allows SMUG1 to, exclude thymine from its active site while accepting HmU.

1OE6 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis] with HMU, GOL and IPA as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OE6 OCA].  

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