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'''Fidelity of Dpo4: effect of metal ions, nucleotide selection and pyrophosphorolysis''' | '''Fidelity of Dpo4: effect of metal ions, nucleotide selection and pyrophosphorolysis''' | ||
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[[Category: Ling, H.]] | [[Category: Ling, H.]] | ||
[[Category: Yang, W.]] | [[Category: Yang, W.]] | ||
[[Category: | [[Category: Base stacking]] | ||
[[Category: | [[Category: Fidelity]] | ||
[[Category: | [[Category: Metal ion]] | ||
[[Category: | [[Category: Mismatch]] | ||
[[Category: | [[Category: Pyrophosphorolysis]] | ||
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Revision as of 19:01, 3 May 2008
Fidelity of Dpo4: effect of metal ions, nucleotide selection and pyrophosphorolysis
OverviewOverview
We report the crystal structures of a translesion DNA polymerase, Dpo4, complexed with a matched or mismatched incoming nucleotide and with a pyrophosphate product after misincorporation. These structures suggest two mechanisms by which Dpo4 may reject a wrong incoming nucleotide with its preformed and open active site. First, a mismatched replicating base pair leads to poor base stacking and alignment of the metal ions and as a consequence, inhibits incorporation. By replacing Mg2+ with Mn2+, which has a relaxed coordination requirement and tolerates misalignment, the catalytic efficiency of misincorporation increases dramatically. Mn2+ also enhances translesion synthesis by Dpo4. Subtle conformational changes that lead to the proper metal ion coordination may, therefore, be a key step in catalysis. Second, the slow release of pyrophosphate may increase the fidelity of Dpo4 by stalling mispaired primer extension and promoting pyrophosphorolysis that reverses the polymerization reaction. Indeed, Dpo4 has robust pyrophosphorolysis activity and degrades the primer strand in the presence of pyrophosphate. The correct incoming nucleotide allows DNA synthesis to overcome pyrophosphorolysis, but an incorrect incoming nucleotide does not.
About this StructureAbout this Structure
2AGO is a Single protein structure of sequence from Sulfolobus solfataricus. Full crystallographic information is available from OCA.
ReferenceReference
Fidelity of Dpo4: effect of metal ions, nucleotide selection and pyrophosphorolysis., Vaisman A, Ling H, Woodgate R, Yang W, EMBO J. 2005 Sep 7;24(17):2957-67. Epub 2005 Aug 18. PMID:16107880 Page seeded by OCA on Sat May 3 19:01:38 2008