Structural highlights
1zyq is a 4 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895 and Bpt7. 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: | 5 (BPT7), trxA, fipA, tsnC ("Bacillus coli" Migula 1895) |
| Activity: | DNA-directed DNA polymerase, with EC number 2.7.7.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[THIO_ECOLI] Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions. [DPOL_BPT7] Replicates viral genomic DNA. Non-processive DNA polymerase that achieves processivity by binding to host thioredoxin (TrxA). This interaction increases the rate of dNTP incorporation to yield a processivity of approximately 800 nucleotides (nt) per binding event. Interacts with DNA helicase gp4 to coordinate nucleotide polymerization with unwinding of the DNA. The leading strand is synthesized continuously while synthesis of the lagging strand requires the synthesis of oligoribonucleotides by the primase domain of gp4.[1] [2]
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
8-oxo-7,8-dihydroguanosine (8oG) is a highly mutagenic DNA lesion that stably pairs with adenosine, forming 8oG(syn).dA(anti) Hoogsteen base pairs. DNA polymerases show different propensities to insert dCMP or dAMP opposite 8oG, but the molecular mechanisms that determine faithful or mutagenic bypass are poorly understood. Here, we report kinetic and structural data providing evidence that, in T7 DNA polymerase, residue Lys536 is responsible for attenuating the miscoding potential of 8oG. The Lys536Ala polymerase shows a significant increase in mutagenic 8oG bypass versus wild-type polymerase, and a crystal structure of the Lys536Ala mutant reveals a closed complex with an 8oG(syn).dATP mismatch in the polymerase active site, in contrast to the unproductive, open complex previously obtained by using wild-type polymerase. We propose that Lys536 acts as a steric and/or electrostatic filter that attenuates the miscoding potential of 8oG by normally interfering with the binding of 8oG in a syn conformation that pairs with dATP.
A lysine residue in the fingers subdomain of T7 DNA polymerase modulates the miscoding potential of 8-oxo-7,8-dihydroguanosine.,Brieba LG, Kokoska RJ, Bebenek K, Kunkel TA, Ellenberger T Structure. 2005 Nov;13(11):1653-9. PMID:16271888[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Notarnicola SM, Mulcahy HL, Lee J, Richardson CC. The acidic carboxyl terminus of the bacteriophage T7 gene 4 helicase/primase interacts with T7 DNA polymerase. J Biol Chem. 1997 Jul 18;272(29):18425-33. PMID:9218486
- ↑ Zhang H, Lee SJ, Zhu B, Tran NQ, Tabor S, Richardson CC. Helicase-DNA polymerase interaction is critical to initiate leading-strand DNA synthesis. Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9372-7. doi:, 10.1073/pnas.1106678108. Epub 2011 May 23. PMID:21606333 doi:http://dx.doi.org/10.1073/pnas.1106678108
- ↑ Brieba LG, Kokoska RJ, Bebenek K, Kunkel TA, Ellenberger T. A lysine residue in the fingers subdomain of T7 DNA polymerase modulates the miscoding potential of 8-oxo-7,8-dihydroguanosine. Structure. 2005 Nov;13(11):1653-9. PMID:16271888 doi:10.1016/j.str.2005.07.020
