1oe6: Difference between revisions
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==Overview== | ==Overview== | ||
Cytosine deamination is a major promutagenic process, generating G:U | 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. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Xenopus laevis]] | [[Category: Xenopus laevis]] | ||
[[Category: Pearl, L | [[Category: Pearl, L H.]] | ||
[[Category: Wibley, J | [[Category: Wibley, J E.A.]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
[[Category: HMU]] | [[Category: HMU]] | ||
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[[Category: smug1]] | [[Category: smug1]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:16:39 2008'' | ||
Revision as of 15:16, 21 February 2008
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XENOPUS SMUG1, AN ANTI-MUTATOR URACIL-DNA GLYCOSYLASE
OverviewOverview
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.
About this StructureAbout this Structure
1OE6 is a Protein complex structure of sequences from Xenopus laevis with , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
ReferenceReference
Structure and specificity of the vertebrate anti-mutator uracil-DNA glycosylase SMUG1., Wibley JE, Waters TR, Haushalter K, Verdine GL, Pearl LH, Mol Cell. 2003 Jun;11(6):1647-59. PMID:12820976
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