1OE6

Xenopus SMUG1, an anti-mutator uracil-DNA Glycosylase

Summary for 1OE6

• Entry DOI: 10.2210/pdb1oe6/pdb
• Related: 1OE4 1OE5
• Descriptor: SINGLE-STRAND SELECTIVE MONOFUNCTIONAL URACIL DNA GLYCOSYLASE, 5'-D(*CP*CP*CP*GP*TP*GP*AP*GP*TP*CP*CP*G)-3', 5'-D(*CP*GP*GP*AP*CP*TP*3DRP*AP*CP*GP*GP*G)-3', ... (7 entities in total)
• Functional Keywords: hydrolase-dna complex, hydrolase, dna glycosylase, single stranded, hydrolase/dna
• Biological source: XENOPUS LAEVIS (AFRICAN CLAWED FROG)
• Cellular location: Nucleus (By similarity): Q9YGN6
• Total number of polymer chains: 4
• Total formula weight: 63147.20

Authors

Wibley, J.E.A.,Pearl, L.H. (deposition date: 2003-03-19, release date: 2003-07-11, Last modification date: 2024-05-01)

Primary citation

Wibley, J.E.A.,Waters, T.R.,Haushalter, K.,Verdine, G.L.,Pearl, L.H.
Structure and Specificity of the Vertebrate Anti-Mutator Uracil-DNA Glycosylase Smug1
Mol.Cell, 11:1647-, 2003

PubMed Abstract: 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.

PubMed: 12820976
DOI: 10.1016/S1097-2765(03)00235-1

Experimental method

X-RAY DIFFRACTION (2.65 Å)