Evidence map›Paper›PMID 21931161›Full record

ArticleThe Journal of biological chemistry2011

Investigation of in vivo diferric tyrosyl radical formation in Saccharomyces cerevisiae Rnr2 protein: requirement of Rnr4 and contribution of Grx3/4 AND Dre2 proteins.

Yan Zhang, Lili Liu, Xiaorong Wu, Xiuxiang An, JoAnne Stubbe, Mingxia Huang

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 49 citations in OpenAlex.

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  19. Conserved electron donor complex Dre2-Tah18 is required for ribonucleotide reductase metallocofactor assembly and DNA synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2014
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Yan ZhangDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Lili LiuDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045.
Xiaorong WuDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045.
Xiuxiang AnDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045.
JoAnne StubbeDepartment of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: stubbe@mit.edu.
Mingxia HuangDepartment of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado 80045. Electronic address: mingxia.huang@ucdenver.edu.
University of Colorado Denver · USMassachusetts Institute of Technology · US

Funding

Ribonucleotide Reductase Regulation: Diferric Y* assembly/maintenance and Sml1R01GM081393 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI STUBBE, JOANNE · 2008 to 2016
$3.9M
NIGMS NIH HHS GM81393NIGMS NIH HHS R01 GM081393
6 · The paper itself

Abstract

The β(2) subunit of class Ia ribonucleotide reductase (RNR) contains a diferric tyrosyl radical cofactor (Fe(2)(III)-Tyr(•)) that is essential for nucleotide reduction. The β(2) subunit of Saccharomyces cerevisiae is a heterodimer of Rnr2 (β) and Rnr4 (β'). Although only β is capable of iron binding and Tyr(•) formation, cells lacking β' are either dead or exhibit extremely low Tyr(•) levels and RNR activity depending on genetic backgrounds. Here, we present evidence supporting the model that β' is required for iron loading and Tyr(•) formation in β in vivo via a pathway that is likely dependent on the cytosolic monothiol glutaredoxins Grx3/Grx4 and the Fe-S cluster protein Dre2. rnr4 mutants are defective in iron loading into nascent β and are hypersensitive to iron depletion and the Tyr(•)-reducing agent hydroxyurea. Transient induction of β' in a GalRNR4 strain leads to a concomitant increase in iron loading and Tyr(•) levels in β. Tyr(•) can also be rapidly generated using endogenous iron when permeabilized Δrnr4 spheroplasts are supplemented with recombinant β' and is inhibited by adding an iron chelator prior to, but not after, β' supplementation. The growth defects of rnr4 mutants are enhanced by deficiencies in grx3/grx4 and dre2. Moreover, depletion of Dre2 in GalDRE2 cells leads to a decrease in both Tyr(•) levels and ββ' activity. This result, in combination with previous findings that a low level of Grx3/4 impairs RNR function, strongly suggests that Grx3/4 and Dre2 serve in the assembly of the deferric Tyr(•) cofactor in RNR.

Indexed as

GlutaredoxinsHydroxyureaIronIron-Sulfur ProteinsMutationOxidoreductasesRibonucleoside Diphosphate ReductaseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSpheroplastsTyrosineDre2 protein, S cerevisiaeGlutaredoxinsGrx3 protein, S cerevisiaeGrx4 protein, S cerevisiaeHydroxyureaIronIron-Sulfur ProteinsOxidoreductasesRibonucleoside Diphosphate ReductaseRnr4 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsTyrosinetyrosyl radical Y(D)

Identifiers

PMID21931161
PMCPMC3308861
OpenAlexW2004256141

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.