Structural highlights
4qwc is a 6 chain structure with sequence from Sacs2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
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| Ligands: | , , |
| NonStd Res: | |
| Related: | |
| Gene: | dbh, dpo4, SSO2448 (SACS2) |
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[DPO4_SACS2] Poorly processive, error-prone DNA polymerase involved in untargeted mutagenesis. Copies undamaged DNA at stalled replication forks, which arise in vivo from mismatched or misaligned primer ends. These misaligned primers can be extended by PolIV. Exhibits no 3'-5' exonuclease (proofreading) activity. It is involved in translesional synthesis.
Publication Abstract from PubMed
Considering that all natural nucleotides (D-dNTPs) and the building blocks (D-dNMPs) of DNA chains possess D-stereochemistry, DNA polymerases and reverse transcriptases (RTs) likely possess strongD-stereoselectivity by preferably binding and incorporating D-dNTPs over unnatural L-dNTPs during DNA synthesis. Surprisingly, a structural basis for the discrimination against L-dNTPs by DNA polymerases or RTs has not been established although L-deoxycytidine analogs (lamivudine and emtricitabine) and L-thymidine (telbivudine) have been widely used as antiviral drugs for years. Here we report seven high-resolution ternary crystal structures of a prototype Y-family DNA polymerase, DNA, and D-dCTP, D-dCDP, L-dCDP, or the diphosphates and triphosphates of lamivudine and emtricitabine. These structures reveal that relative to D-dCTP, each of these L-nucleotides has its sugar ring rotated by 180 degrees with an unusual O4'-endo sugar puckering and exhibits multiple triphosphate-binding conformations within the active site of the polymerase. Such rare binding modes significantly decrease the incorporation rates and efficiencies of these L-nucleotides catalyzed by the polymerase.
Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase.,Gaur V, Vyas R, Fowler JD, Efthimiopoulos G, Feng JY, Suo Z Nucleic Acids Res. 2014 Aug 7. pii: gku709. PMID:25104018[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gaur V, Vyas R, Fowler JD, Efthimiopoulos G, Feng JY, Suo Z. Structural and kinetic insights into binding and incorporation of L-nucleotide analogs by a Y-family DNA polymerase. Nucleic Acids Res. 2014 Aug 7. pii: gku709. PMID:25104018 doi:http://dx.doi.org/10.1093/nar/gku709
