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Categories containing this gene/protein


transcription factors and their control, resistance against oxidative and electrophile stress

This gene is a member of the following regulons


PerR regulon

The PerR regulon


Gene


  • Coordinates on the chromosome (coding sequence): 944,487 -> 944,924
  • Phenotypes of a mutant

  • resistant to hydrogen peroxide, accumulates a porphyrin-like compound, and grows very slowly (due to heme sequestration by KatA) PubMed
  • The protein


    Catalyzed reaction/ biological activity

    Protein family

  • Fur family
  • Paralogous protein(s)

  • Zur, Fur
  • Kinetic information

    Domains

    Modification

  • selective metal catalyzed oxidation of two histidine residues of the regulatory site results in induction (loss of DNA-binding activity) PubMed
  • Cofactors

  • contains an Fe(2+) at the regulatory site and Zn(2+) PubMed
  • Effectors of protein activity

  • responds to the presence of hydrogen peroxide
  • Structure

  • 2RGV 3F8N
  • Localization

  • cytoplasm (according to Swiss-Prot)
  • Interactions

    Additional information

    Expression and Regulation


    Operon

  • perR PubMed
  • Sigma factor

  • SigA PubMed
  • Regulation

  • negative autoregulation PubMed
  • induced in the presence of hydrogen peroxide (PerR) PubMed
  • Regulatory mechanism

  • PerR: transcription repression PubMed
  • Additional information

    Biological materials


    Mutant

  • MGNA-A258 (ygaG::erm), available at the NBRP B. subtilis, Japan
  • HB0509 (spc), available in John Helmanns and Jörg Stülkes labs, also GP868 (fur::mls, perR::spc).
  • 1A903 ( perR::kan), PubMed, available at the Bacillus Genetic Stock Center
  • BKE08730 (perR::erm trpC2) is available at the Bacillus Genetic Stock Center
  • Expression vector

    lacZ fusion

    GFP fusion

    two-hybrid system

    FLAG-tag construct

    Antibody

    Labs working on this gene/protein


  • John Helmann, Cornell University, USA Homepage
  • References


    Reviews

    Ahn BE, Baker TA

    Oxidization without substrate unfolding triggers proteolysis of the peroxide-sensor, PerR

    Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E23-31. doi: 10.1073/pnas.1522687112. Epub 2015 Dec 17. PubMed PMID: 26677871; PubMed Central PMCID: PMC4711837.
    Imlay JA

    Transcription Factors That Defend Bacteria Against Reactive Oxygen Species

    Annu Rev Microbiol. 2015;69:93-108. doi: 10.1146/annurev-micro-091014-104322. Epub 2015 Jun 11. Review. PubMed PMID: 26070785; PubMed Central PMCID: PMC4618077.
    Helmann JD

    Specificity of metal sensing: iron and manganese homeostasis in Bacillus subtilis

    J Biol Chem. 2014 Oct 10;289(41):28112-20. doi: 10.1074/jbc.R114.587071. Epub 2014 Aug 26. Review. PubMed PMID: 25160631; PubMed Central PMCID: PMC4192466.
    Dubbs JM, Mongkolsuk S

    Peroxide-sensing transcriptional regulators in bacteria

    J Bacteriol. 2012 Oct;194(20):5495-503. Epub 2012 Jul 13. Review. PubMed PMID: 22797754; PubMed Central PMCID: PMC3458676.
    Faulkner MJ, Helmann JD

    Peroxide stress elicits adaptive changes in bacterial metal ion homeostasis

    Antioxid Redox Signal. 2011 Jul 1;15(1):175-89. doi: 10.1089/ars.2010.3682. Epub 2011 Apr 10. Review. PubMed PMID: 20977351; PubMed Central PMCID: PMC3110094.
    Duarte V, Latour JM

    PerR vs OhrR: selective peroxide sensing in Bacillus subtilis

    Mol Biosyst. 2010 Feb;6(2):316-23. doi: 10.1039/b915042k. Epub 2009 Sep 18. Review. PubMed PMID: 20094649.
    Zuber P

    Management of oxidative stress in Bacillus

    Annu Rev Microbiol. 2009;63:575-97. doi: 10.1146/annurev.micro.091208.073241. Review. PubMed PMID: 19575568.
    Giedroc DP

    Hydrogen peroxide sensing in Bacillus subtilis: it is all about the (metallo)regulator

    Mol Microbiol. 2009 Jul;73(1):1-4. doi: 10.1111/j.1365-2958.2009.06752.x. Epub 2009 Jun 8. PubMed PMID: 19508286; PubMed Central PMCID: PMC2765198.

    Original Publications

    Kim JH, Won YB, Ji CJ, Yang YM, Ryu SH, Ju SY, Kwon Y, Lee YE, Lee JW

    The difference in in vivo sensitivity between Bacillus licheniformis PerR and Bacillus subtilis PerR is due to the different cellular environments

    Biochem Biophys Res Commun. 2017 Feb 26;484(1):125-131. doi: 10.1016/j.bbrc.2017.01.060. Epub 2017 Jan 16. PubMed PMID: 28104400.
    Chandrangsu P, Helmann JD

    Intracellular Zn(II) Intoxication Leads to Dysregulation of the PerR Regulon Resulting in Heme Toxicity in Bacillus subtilis

    PLoS Genet. 2016 Dec 9;12(12):e1006515. doi: 10.1371/journal.pgen.1006515. eCollection 2016 Dec. PubMed PMID: 27935957; PubMed Central PMCID: PMC5189952.
    Castro-Cerritos KV, Yasbin RE, Robleto EA, Pedraza-Reyes M

    Role of Ribonucleotide Reductase in Bacillus subtilis Stress-Associated Mutagenesis

    J Bacteriol. 2017 Jan 30;199(4). pii: e00715-16. doi: 10.1128/JB.00715-16. Print 2017 Feb 15. PubMed PMID: 27920297; PubMed Central PMCID: PMC5287397.
    Guan G, Pinochet-Barros A, Gaballa A, Patel SJ, Argüello JM, Helmann JD

    PfeT, a P1B4 -type ATPase, effluxes ferrous iron and protects Bacillus subtilis against iron intoxication

    Mol Microbiol. 2015 Nov;98(4):787-803. doi: 10.1111/mmi.13158. Epub 2015 Sep 10. PubMed PMID: 26261021; PubMed Central PMCID: PMC4648274.
    Caux-Thang C, Parent A, Sethu R, Maïga A, Blondin G, Latour JM, Duarte V

    Single asparagine to arginine mutation allows PerR to switch from PerR box to fur box

    ACS Chem Biol. 2015 Mar 20;10(3):682-6. doi: 10.1021/cb500783g. Epub 2014 Dec 11. PubMed PMID: 25486128.
    Yang CK, Tai PC, Lu CD

    Time-related transcriptome analysis of B

    subtilis 168 during growth with glucose. Curr Microbiol. 2014 Jan;68(1):12-20. doi: 10.1007/s00284-013-0432-4. Epub 2013 Aug 10. PubMed PMID: 23934352.
    Makthal N, Rastegari S, Sanson M, Ma Z, Olsen RJ, Helmann JD, Musser JM, Kumaraswami M

    Crystal structure of peroxide stress regulator from Streptococcus pyogenes provides functional insights into the mechanism of oxidative stress sensing

    J Biol Chem. 2013 Jun 21;288(25):18311-24. doi: 10.1074/jbc.M113.456590. Epub 2013 May 3. PubMed PMID: 23645680; PubMed Central PMCID: PMC3689973.
    Ma Z, Faulkner MJ, Helmann JD

    Origins of specificity and cross-talk in metal ion sensing by Bacillus subtilis Fur

    Mol Microbiol. 2012 Dec;86(5):1144-55. doi: 10.1111/mmi.12049. Epub 2012 Oct 12. PubMed PMID: 23057863; PubMed Central PMCID: PMC3508374.
    Faulkner MJ, Ma Z, Fuangthong M, Helmann JD

    Derepression of the Bacillus subtilis PerR peroxide stress response leads to iron deficiency

    J Bacteriol. 2012 Mar;194(5):1226-35. doi: 10.1128/JB.06566-11. Epub 2011 Dec 22. PubMed PMID: 22194458; PubMed Central PMCID: PMC3294777.
    Ma Z, Lee JW, Helmann JD

    Identification of altered function alleles that affect Bacillus subtilis PerR metal ion selectivity

    Nucleic Acids Res. 2011 Jul;39(12):5036-44. doi: 10.1093/nar/gkr095. Epub 2011 Mar 11. PubMed PMID: 21398634; PubMed Central PMCID: PMC3130269.
    Jacquamet L, Traoré DA, Ferrer JL, Proux O, Testemale D, Hazemann JL, Nazarenko E, El Ghazouani A, Caux-Thang C, Duarte V, Latour JM

    Structural characterization of the active form of PerR: insights into the metal-induced activation of PerR and Fur proteins for DNA binding

    Mol Microbiol. 2009 Jul;73(1):20-31. doi: 10.1111/j.1365-2958.2009.06753.x. Epub 2009 Jun 8. PubMed PMID: 19508285.
    Hochgräfe F, Wolf C, Fuchs S, Liebeke M, Lalk M, Engelmann S, Hecker M

    Nitric oxide stress induces different responses but mediates comparable protein thiol protection in Bacillus subtilis and Staphylococcus aureus

    J Bacteriol. 2008 Jul;190(14):4997-5008. doi: 10.1128/JB.01846-07. Epub 2008 May 16. PubMed PMID: 18487332; PubMed Central PMCID: PMC2447014.
    Leelakriangsak M, Kobayashi K, Zuber P

    Dual negative control of spx transcription initiation from the P3 promoter by repressors PerR and YodB in Bacillus subtilis

    J Bacteriol. 2007 Mar;189(5):1736-44. Epub 2006 Dec 8. PubMed PMID: 17158660; PubMed Central PMCID: PMC1855716.
    Lee JW, Helmann JD

    Biochemical characterization of the structural Zn2+ site in the Bacillus subtilis peroxide sensor PerR

    J Biol Chem. 2006 Aug 18;281(33):23567-78. Epub 2006 Jun 8. PubMed PMID: 16766519.
    Lee JW, Helmann JD

    The PerR transcription factor senses H2O2 by metal-catalysed histidine oxidation

    Nature. 2006 Mar 16;440(7082):363-7. PubMed PMID: 16541078.
    Hayashi K, Ohsawa T, Kobayashi K, Ogasawara N, Ogura M

    The H2O2 stress-responsive regulator PerR positively regulates srfA expression in Bacillus subtilis

    J Bacteriol. 2005 Oct;187(19):6659-67. PubMed PMID: 16166527; PubMed Central PMCID: PMC1251593.
    Moore CM, Nakano MM, Wang T, Ye RW, Helmann JD

    Response of Bacillus subtilis to nitric oxide and the nitrosating agent sodium nitroprusside

    J Bacteriol. 2004 Jul;186(14):4655-64. PubMed PMID: 15231799; PubMed Central PMCID: PMC438601.
    Fuangthong M, Helmann JD

    Recognition of DNA by three ferric uptake regulator (Fur) homologs in Bacillus subtilis

    J Bacteriol. 2003 Nov;185(21):6348-57. PubMed PMID: 14563870; PubMed Central PMCID: PMC219410.
    Helmann JD, Wu MF, Gaballa A, Kobel PA, Morshedi MM, Fawcett P, Paddon C

    The global transcriptional response of Bacillus subtilis to peroxide stress is coordinated by three transcription factors

    J Bacteriol. 2003 Jan;185(1):243-53. PubMed PMID: 12486061; PubMed Central PMCID: PMC141929.
    Fuangthong M, Herbig AF, Bsat N, Helmann JD

    Regulation of the Bacillus subtilis fur and perR genes by PerR: not all members of the PerR regulon are peroxide inducible

    J Bacteriol. 2002 Jun;184(12):3276-86. PubMed PMID: 12029044; PubMed Central PMCID: PMC135084.
    Fuangthong M, Herbig AF, Bsat N, Helmann JD

    Regulation of the Bacillus subtilis fur and perR genes by PerR: not all members of the PerR regulon are peroxide inducible

    J Bacteriol. 2002 Jun;184(12):3276-86. PubMed PMID: 12029044; PubMed Central PMCID: PMC135084.
    Fuangthong M, Herbig AF, Bsat N, Helmann JD

    Regulation of the Bacillus subtilis fur and perR genes by PerR: not all members of the PerR regulon are peroxide inducible

    J Bacteriol. 2002 Jun;184(12):3276-86. PubMed PMID: 12029044; PubMed Central PMCID: PMC135084.
    Herbig AF, Helmann JD

    Roles of metal ions and hydrogen peroxide in modulating the interaction of the Bacillus subtilis PerR peroxide regulon repressor with operator DNA

    Mol Microbiol. 2001 Aug;41(4):849-59. PubMed PMID: 11532148.
    Herbig AF, Helmann JD

    Roles of metal ions and hydrogen peroxide in modulating the interaction of the Bacillus subtilis PerR peroxide regulon repressor with operator DNA

    Mol Microbiol. 2001 Aug;41(4):849-59. PubMed PMID: 11532148.
    Casillas-Martinez L, Driks A, Setlow B, Setlow P

    Lack of a significant role for the PerR regulator in Bacillus subtilis spore resistance

    FEMS Microbiol Lett. 2000 Jul 15;188(2):203-8. PubMed PMID: 10913706.
    Bsat N, Herbig A, Casillas-Martinez L, Setlow P, Helmann JD

    Bacillus subtilis contains multiple Fur homologues: identification of the iron uptake (Fur) and peroxide regulon (PerR) repressors

    Mol Microbiol. 1998 Jul;29(1):189-98. PubMed PMID: 9701813.
    Bsat N, Chen L, Helmann JD

    Mutation of the Bacillus subtilis alkyl hydroperoxide reductase (ahpCF) operon reveals compensatory interactions among hydrogen peroxide stress genes

    J Bacteriol. 1996 Nov;178(22):6579-86. PubMed PMID: 8932315; PubMed Central PMCID: PMC178545.
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