ArticleThe Journal of biological chemistry2008
Chemical and traditional mutagenesis of vaccinia DNA topoisomerase provides insights to cleavage site recognition and transesterification chemistry.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Mechanism of negative supercoil relaxation by Topoisomerase IV.Nucleic acids research · 2026Article
- Deletions initiated by the vaccinia virus TopIB protein in yeast.DNA repair · 2024Article
- Site-Selective Tyrosine Phosphorylation in the Activation of the p50 Subunit of NF-κB for DNA Binding and Transcription.ACS chemical biology · 2023Article
- Development of a Novel Biosensor-Driven Mutation and Selection System viaFrontiers in bioengineering and biotechnology · 2020Article
- Characterization of DNA Binding by the Isolated N-Terminal Domain of Vaccinia Virus DNA Topoisomerase IB.Biochemistry · 2017Article
- Article
- Nanoblinker: Brownian motion powered bio-nanomachine for FRET detection of phagocytic phase of apoptosis.PloS one · 2014Article
- Chemical mutagenesis of vaccinia DNA topoisomerase lysine 167 provides insights to the catalysis of DNA transesterification.Biochemistry · 2013Article
- Synthesis of pdCpAs and transfer RNAs activated with thiothreonine and derivatives.Bioorganic & medicinal chemistry · 2012Article
- Nucleases: diversity of structure, function and mechanism.Quarterly reviews of biophysics · 2011Review
- Requirements for catalysis in the Cre recombinase active site.Nucleic acids research · 2010Article
- Crystal structure of a bacterial topoisomerase IB in complex with DNA reveals a secondary DNA binding site.Structure (London, England : 1993) · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Vaccinia DNA topoisomerase IB (TopIB) relaxes supercoils by forming and resealing a covalent DNA-(3'-phosphotyrosyl)-enzyme intermediate. Here we gained new insights to the TopIB mechanism through "chemical mutagenesis." Meta-substituted analogs of Tyr(274) were introduced by in vitro translation in the presence of a chemically misacylated tRNA. We report that a meta-OH reduced the rate of DNA cleavage 130-fold without affecting the rate of religation. By contrast, meta-OCH(3) and NO(2) groups elicited only a 6-fold decrement in cleavage rate. We propose that the meta-OH uniquely suppresses deprotonation of the para-OH nucleophile during the cleavage step. Assembly of the vaccinia TopIB active site is triggered by protein contacts with a specific DNA sequence 5'-C(+5)C(+4)C(+3)T(+2)T(+1)p downward arrowN (where downward arrow denotes the cleavage site). A signature alpha-helix of the poxvirus TopIB ((132)GKMKYLKENETVG(144)) engages the target site in the major groove and thereby recruits catalytic residue Arg(130) to the active site. The effects of 11 missense mutations at Tyr(136) highlight the importance of van der Waals interactions with the 3'-G(+4)pG(+3)p dinucleotide of the nonscissile strand for DNA cleavage and supercoil relaxation. Asn(140) and Thr(142) donate hydrogen bonds to the pro-(S(p))-oxygen of the G(+3)pA(+2) phosphodiester of the nonscissile strand. Lys(133) and Lys(135) interact with purine nucleobases in the major groove. Whereas none of these side chains is essential per se, an N140A/T142A double mutation reduces the rate of supercoil relaxation and DNA cleavage by 120- and 30-fold, respectively, and a K133A/K135A double mutation slows relaxation and cleavage by 120- and 35-fold, respectively. These results underscore functional redundancy at the TopIB-DNA interface.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.