WHIB1_MYCTU
ID WHIB1_MYCTU Reviewed; 84 AA.
AC P9WF43; F2GK92; L0TEP0; O05847; Q7D5W8;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Transcriptional regulator WhiB1;
GN Name=whiB1; OrderedLocusNames=Rv3219;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15882420; DOI=10.1111/j.1365-2958.2005.04609.x;
RA Rickman L., Scott C., Hunt D.M., Hutchinson T., Menendez M.C., Whalan R.,
RA Hinds J., Colston M.J., Green J., Buxton R.S.;
RT "A member of the cAMP receptor protein family of transcription regulators
RT in Mycobacterium tuberculosis is required for virulence in mice and
RT controls transcription of the rpfA gene coding for a resuscitation
RT promoting factor.";
RL Mol. Microbiol. 56:1274-1286(2005).
RN [3]
RP FUNCTION AS A PROTEIN DISULFIDE REDUCTASE, BIOPHYSICOCHEMICAL PROPERTIES,
RP MASS SPECTROMETRY, SUBUNIT, AND DISULFIDE BONDS.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17157031; DOI=10.1016/j.pep.2006.10.015;
RA Garg S.K., Suhail Alam M., Soni V., Radha Kishan K.V., Agrawal P.;
RT "Characterization of Mycobacterium tuberculosis WhiB1/Rv3219 as a protein
RT disulfide reductase.";
RL Protein Expr. Purif. 52:422-432(2007).
RN [4]
RP INTERACTION WITH GLGB.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19121228; DOI=10.1186/1471-2091-10-1;
RA Garg S., Alam M.S., Bajpai R., Kishan K.R., Agrawal P.;
RT "Redox biology of Mycobacterium tuberculosis H37Rv: protein-protein
RT interaction between GlgB and WhiB1 involves exchange of thiol-disulfide.";
RL BMC Biochem. 10:1-1(2009).
RN [5]
RP FUNCTION AS A PROTEIN DISULFIDE REDUCTASE, COFACTOR, AND DISULFIDE BOND.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19016840; DOI=10.1111/j.1742-4658.2008.06755.x;
RA Alam M.S., Garg S.K., Agrawal P.;
RT "Studies on structural and functional divergence among seven WhiB proteins
RT of Mycobacterium tuberculosis H37Rv.";
RL FEBS J. 276:76-93(2009).
RN [6]
RP FUNCTION, COFACTOR, DINITROSYLATION, DNA-BINDING, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20929442; DOI=10.1042/bj20101440;
RA Smith L.J., Stapleton M.R., Fullstone G.J., Crack J.C., Thomson A.J.,
RA Le Brun N.E., Hunt D.M., Harvey E., Adinolfi S., Buxton R.S., Green J.;
RT "Mycobacterium tuberculosis WhiB1 is an essential DNA-binding protein with
RT a nitric oxide-sensitive iron-sulfur cluster.";
RL Biochem. J. 432:417-427(2010).
RN [7]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20028978; DOI=10.1074/jbc.m109.047720;
RA Stapleton M., Haq I., Hunt D.M., Arnvig K.B., Artymiuk P.J., Buxton R.S.,
RA Green J.;
RT "Mycobacterium tuberculosis cAMP receptor protein (Rv3676) differs from the
RT Escherichia coli paradigm in its cAMP binding and DNA binding properties
RT and transcription activation properties.";
RL J. Biol. Chem. 285:7016-7027(2010).
RN [8]
RP DINITROSYLATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21182249; DOI=10.1021/ja109581t;
RA Crack J.C., Smith L.J., Stapleton M.R., Peck J., Watmough N.J.,
RA Buttner M.J., Buxton R.S., Green J., Oganesyan V.S., Thomson A.J.,
RA Le Brun N.E.;
RT "Mechanistic insight into the nitrosylation of the [4Fe-4S] cluster of
RT WhiB-like proteins.";
RL J. Am. Chem. Soc. 133:1112-1121(2011).
RN [9]
RP MUTAGENESIS OF CYS-9; ASP-13; CYS-37; CYS-40; CYS-46; SER-57; GLY-58;
RP VAL-59; TRP-60; GLY-61; GLY-62; LYS-72; ARG-73; ARG-74; LYS-79 AND ARG-81.
RX PubMed=22792304; DOI=10.1371/journal.pone.0040407;
RA Smith L.J., Stapleton M.R., Buxton R.S., Green J.;
RT "Structure-function relationships of the Mycobacterium tuberculosis
RT transcription factor WhiB1.";
RL PLoS ONE 7:E40407-E40407(2012).
RN [10]
RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND DNA-BINDING.
RX PubMed=22464736; DOI=10.1016/j.tube.2012.03.001;
RA Stapleton M.R., Smith L.J., Hunt D.M., Buxton R.S., Green J.;
RT "Mycobacterium tuberculosis WhiB1 represses transcription of the essential
RT chaperonin GroEL2.";
RL Tuberculosis 92:328-332(2012).
CC -!- FUNCTION: Acts as a transcriptional repressor, inhibiting expression in
CC vitro. Probably redox-responsive. The apo- but not holo-form binds to
CC its own promoter as well as that of groEL2. Oxidized apo-form and
CC nitrosylated holo-form also bind DNA. The apo-form has been shown to
CC act as a protein disulfide reductase (PubMed:17157031)
CC (PubMed:19016840), but also not to act as a protein disulfide reductase
CC (PubMed:20929442). {ECO:0000269|PubMed:17157031,
CC ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:20929442,
CC ECO:0000269|PubMed:22464736}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:20929442};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. This cluster is stable to
CC O(2) but very reactive to nitric oxide (NO). Following nitrosylation of
CC the [4Fe-4S] cluster binds 1 [4Fe-8(NO)] cluster per subunit.
CC {ECO:0000269|PubMed:19016840, ECO:0000269|PubMed:20929442};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Redox potential:
CC E(0) is -236 +/-2 mV. {ECO:0000269|PubMed:17157031};
CC -!- SUBUNIT: Homodimer. Interacts with GlgB via an intermolecular disulfide
CC bond. {ECO:0000269|PubMed:17157031, ECO:0000269|PubMed:19121228}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- INDUCTION: Activated by CRP. Essentially constitutive over all growth
CC phases. 2-fold induced by ethanol, repressed by SDS and heat shock. Not
CC induced by hypoxia, slightly induced by NO and in macrophage and mouse
CC infection, 10-fold induced by cAMP. There are 2 CRP-binding sites in
CC the promoter of whiB1, at low concentrations of CRP with or without
CC cAMP transcription of whiB1 is enhanced via site CRP1, then repressed
CC as site CRP2 is filled. {ECO:0000269|PubMed:15882420,
CC ECO:0000269|PubMed:20028978}.
CC -!- PTM: Can be nitrosylated by NO, 8 NO react per cluster leading to the
CC formation of 2 dinitrosyliron thiol complexes (DNIC). These complexes
CC are quite stable in the presence of air.
CC -!- PTM: Upon aerobic 4Fe-4S cluster removal intramolecular disulfide bonds
CC are formed.
CC -!- MASS SPECTROMETRY: Mass=14055.33; Method=MALDI; Note=Fully oxidized
CC recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:17157031};
CC -!- MASS SPECTROMETRY: Mass=14284.25; Method=MALDI; Note=For fully
CC alkylated recombinant protein tagged at both termini.;
CC Evidence={ECO:0000269|PubMed:17157031};
CC -!- DISRUPTION PHENOTYPE: Essential. {ECO:0000269|PubMed:20929442}.
CC -!- SIMILARITY: Belongs to the WhiB family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AL123456; CCP46035.1; -; Genomic_DNA.
DR PIR; D70596; D70596.
DR RefSeq; NP_217735.1; NC_000962.3.
DR RefSeq; WP_003416884.1; NZ_NVQJ01000003.1.
DR PDB; 5OAY; NMR; -; A=1-84.
DR PDB; 6ONO; X-ray; 1.85 A; A/C=1-76.
DR PDB; 6ONU; X-ray; 1.85 A; A/C/E/G=1-76.
DR PDBsum; 5OAY; -.
DR PDBsum; 6ONO; -.
DR PDBsum; 6ONU; -.
DR AlphaFoldDB; P9WF43; -.
DR SMR; P9WF43; -.
DR STRING; 83332.Rv3219; -.
DR PaxDb; P9WF43; -.
DR DNASU; 887980; -.
DR GeneID; 45427212; -.
DR GeneID; 887980; -.
DR KEGG; mtu:Rv3219; -.
DR TubercuList; Rv3219; -.
DR eggNOG; ENOG5032RSG; Bacteria.
DR OMA; DTCLKWA; -.
DR PhylomeDB; P9WF43; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:MTBBASE.
DR GO; GO:0035731; F:dinitrosyl-iron complex binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IDA:MTBBASE.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0047134; F:protein-disulfide reductase (NAD(P)) activity; IDA:MTBBASE.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:MTBBASE.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CACAO.
DR GO; GO:0071731; P:response to nitric oxide; IDA:MTBBASE.
DR HAMAP; MF_01479; WhiB; 1.
DR InterPro; IPR034768; 4FE4S_WBL.
DR InterPro; IPR003482; Whib.
DR PANTHER; PTHR38839; PTHR38839; 1.
DR Pfam; PF02467; Whib; 1.
DR PROSITE; PS51674; 4FE4S_WBL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Cytoplasm; Disulfide bond; DNA-binding; Iron;
KW Iron-sulfur; Metal-binding; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..84
FT /note="Transcriptional regulator WhiB1"
FT /id="PRO_0000420379"
FT DOMAIN 8..70
FT /note="4Fe-4S Wbl-type"
FT BINDING 9
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 37
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 40
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT BINDING 46
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT MUTAGEN 9
FT /note="C->A: Does not bind 4Fe-4S cluster, binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 13
FT /note="D->A: No change in 4Fe-4S cluster, binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 37
FT /note="C->A: Does not bind 4Fe-4S cluster, binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 40
FT /note="C->A: Does not bind 4Fe-4S cluster, binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 46
FT /note="C->A: Does not bind 4Fe-4S cluster, binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 57
FT /note="S->E: Still binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 58
FT /note="G->E: Loss of DNA-binding, still binds 4Fe-4S
FT cluster."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 59
FT /note="V->E: Still binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 60
FT /note="W->E: Still binds DNA."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 61
FT /note="G->E: Loss of DNA-binding, still binds 4Fe-4S
FT cluster."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 62
FT /note="G->E: Loss of DNA-binding, still binds 4Fe-4S
FT cluster."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 72
FT /note="K->E: Loss of 4Fe-4S cluster, loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 73
FT /note="R->E: Loss of 4Fe-4S cluster, loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 74
FT /note="R->E: Loss of 4Fe-4S cluster, loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 79
FT /note="K->E: Loss of 4Fe-4S cluster, loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:22792304"
FT MUTAGEN 81
FT /note="R->E: Loss of 4Fe-4S cluster, loss of DNA-binding."
FT /evidence="ECO:0000269|PubMed:22792304"
FT HELIX 3..6
FT /evidence="ECO:0007829|PDB:6ONO"
FT HELIX 8..11
FT /evidence="ECO:0007829|PDB:6ONO"
FT HELIX 14..17
FT /evidence="ECO:0007829|PDB:6ONO"
FT STRAND 22..24
FT /evidence="ECO:0007829|PDB:6ONO"
FT HELIX 27..38
FT /evidence="ECO:0007829|PDB:6ONO"
FT HELIX 43..53
FT /evidence="ECO:0007829|PDB:6ONO"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:5OAY"
FT HELIX 65..71
FT /evidence="ECO:0007829|PDB:6ONO"
SQ SEQUENCE 84 AA; 9319 MW; E06C6D18F7C31ED2 CRC64;
MDWRHKAVCR DEDPELFFPV GNSGPALAQI ADAKLVCNRC PVTTECLSWA LNTGQDSGVW
GGMSEDERRA LKRRNARTKA RTGV
