| Structural highlights
2w9a is a 3 chain structure with sequence from Sulfolobus solfataricus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| NonStd Res: | , |
| Related: | 1s0m, 2asl, 2jeg, 1rys, 2v4s, 2j6t, 1n56, 2w9b, 1jx4, 2atl, 2c22, 2va2, 1s97, 2agq, 2ago, 2jej, 2asj, 2w9c, 2asd, 1jxl, 1n48, 2bq3, 2j6u, 2uvu, 2agp, 1s0n, 2c2r, 2w8l, 2jef, 1s0o, 2uvw, 2bqr, 2jei, 2bqu, 2au0, 1s9f, 2c28, 2v9w, 2v4r, 2c2e, 1ryr, 2uvv, 2c2d, 2v4q, 1s10, 2j6s, 2br0, 2uvr, 2va3, 2w8k, 2v4t |
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Previous work has shown that Y-family DNA polymerases tolerate large DNA adducts, but a substantial decrease in catalytic efficiency and fidelity occurs during bypass of N(2),N(2)-dimethyl (Me(2))-substituted guanine (N(2),N(2)-Me(2)G), in contrast to a single methyl substitution. Therefore, it is unclear why the addition of two methyl groups is so disruptive. The presence of N(2),N(2)-Me(2)G lowered the catalytic efficiency of the model enzyme Sulfolobus solfataricus Dpo4 16,000-fold. Dpo4 inserted dNTPs almost at random during bypass of N(2),N(2)-Me(2)G, and much of the enzyme was kinetically trapped by an inactive ternary complex when N(2),N(2)-Me(2)G was present, as judged by a reduced burst amplitude (5% of total enzyme) and kinetic modeling. One crystal structure of Dpo4 with a primer having a 3'-terminal dideoxycytosine (C(dd)) opposite template N(2),N(2)-Me(2)G in a post-insertion position showed C(dd) folded back into the minor groove, as a catalytically incompetent complex. A second crystal had two unique orientations for the primer terminal C(dd) as follows: (i) flipped into the minor groove and (ii) a long pairing with N(2),N(2)-Me(2)G in which one hydrogen bond exists between the O-2 atom of C(dd) and the N-1 atom of N(2),N(2)-Me(2)G, with a second water-mediated hydrogen bond between the N-3 atom of C(dd) and the O-6 atom of N(2),N(2)-Me(2)G. A crystal structure of Dpo4 with dTTP opposite template N(2),N(2)-Me(2)G revealed a wobble orientation. Collectively, these results explain, in a detailed manner, the basis for the reduced efficiency and fidelity of Dpo4-catalyzed bypass of N(2),N(2)-Me(2)G compared with mono-substituted N(2)-alkyl G adducts.
Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES.,Zhang H, Eoff RL, Kozekov ID, Rizzo CJ, Egli M, Guengerich FP J Biol Chem. 2009 Jun 26;284(26):17687-99. PMID:19542237[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang H, Eoff RL, Kozekov ID, Rizzo CJ, Egli M, Guengerich FP. Structure-Function Relationships in Miscoding by Sulfolobus solfataricus DNA Polymerase Dpo4: GUANINE N2,N2-DIMETHYL SUBSTITUTION PRODUCES INACTIVE AND MISCODING POLYMERASE COMPLEXES. J Biol Chem. 2009 Jun 26;284(26):17687-99. PMID:19542237 doi:284/26/17687
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