DOST_MYCTU
ID DOST_MYCTU Reviewed; 573 AA.
AC P9WGK1; L0TB49; O53473; Q7D7L6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=Oxygen sensor histidine kinase response regulator DosT {ECO:0000303|PubMed:28977726};
DE EC=2.7.13.3 {ECO:0000269|PubMed:15033981};
GN Name=dosT; OrderedLocusNames=Rv2027c;
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 FUNCTION, PHOSPHORYLATION AT HIS-392, HEME COFACTOR, COFACTOR, INDUCTION,
RP AND MUTAGENESIS OF HIS-392.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15135056; DOI=10.1016/j.febslet.2004.02.092;
RA Saini D.K., Malhotra V., Tyagi J.S.;
RT "Cross talk between DevS sensor kinase homologue, Rv2027c, and DevR
RT response regulator of Mycobacterium tuberculosis.";
RL FEBS Lett. 565:75-80(2004).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 329-HIS--HIS-394.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15033981; DOI=10.1074/jbc.m401230200;
RA Roberts D.M., Liao R.P., Wisedchaisri G., Hol W.G., Sherman D.R.;
RT "Two sensor kinases contribute to the hypoxic response of Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 279:23082-23087(2004).
RN [4]
RP FUNCTION AS A HYPOXIA SENSOR, LIGAND-BINDING, AND HEME COFACTOR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17609369; DOI=10.1073/pnas.0705054104;
RA Kumar A., Toledo J.C., Patel R.P., Lancaster J.R. Jr., Steyn A.J.;
RT "Mycobacterium tuberculosis DosS is a redox sensor and DosT is a hypoxia
RT sensor.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:11568-11573(2007).
RN [5]
RP FUNCTION AS AN OXYGEN SENSOR, HEME COFACTOR, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, SUBCELLULAR LOCATION, AND LIGAND-BINDING.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17600145; DOI=10.1110/ps.072897707;
RA Sousa E.H., Tuckerman J.R., Gonzalez G., Gilles-Gonzalez M.A.;
RT "DosT and DevS are oxygen-switched kinases in Mycobacterium tuberculosis.";
RL Protein Sci. 16:1708-1719(2007).
RN [6]
RP FUNCTION IN CARBON MONOXIDE (CO) RESPONSE, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007;
RA Shiloh M.U., Manzanillo P., Cox J.S.;
RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during
RT macrophage infection.";
RL Cell Host Microbe 3:323-330(2008).
RN [7]
RP FUNCTION IN CARBON MONOXIDE (CO) RESPONSE, DISRUPTION PHENOTYPE, AND
RP DORMANCY REGULON.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18400743; DOI=10.1074/jbc.m802274200;
RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., Kramnik I.,
RA Agarwal A., Steyn A.J.;
RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium
RT tuberculosis dormancy regulon.";
RL J. Biol. Chem. 283:18032-18039(2008).
RN [8]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=H37Rv;
RX PubMed=19487478; DOI=10.1128/iai.01449-08;
RA Honaker R.W., Leistikow R.L., Bartek I.L., Voskuil M.I.;
RT "Unique roles of DosT and DosS in DosR regulon induction and Mycobacterium
RT tuberculosis dormancy.";
RL Infect. Immun. 77:3258-3263(2009).
RN [9]
RP MUTAGENESIS OF GLY-85.
RC STRAIN=H37Rv;
RX PubMed=21536032; DOI=10.1016/j.febslet.2011.04.050;
RA Cho H.Y., Cho H.J., Kim M.H., Kang B.S.;
RT "Blockage of the channel to heme by the E87 side chain in the GAF domain of
RT Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to
RT oxygen.";
RL FEBS Lett. 585:1873-1878(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [11]
RP FUNCTION, AND COFACTOR.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=28977726; DOI=10.1111/febs.14284;
RA Sousa E.H.S., Gonzalez G., Gilles-Gonzalez M.A.;
RT "Target DNA stabilizes Mycobacterium tuberculosis DevR/DosR phosphorylation
RT by the full-length oxygen sensors DevS/DosS and DosT.";
RL FEBS J. 284:3954-3967(2017).
RN [12]
RP REVIEW.
RX PubMed=25002970; DOI=10.3390/bios3030259;
RA Sivaramakrishnan S., de Montellano P.R.;
RT "The DosS-DosT/DosR mycobacterial sensor system.";
RL Biosensors 3:259-282(2013).
RN [13] {ECO:0007744|PDB:2VZW}
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 61-208 IN COMPLEX WITH HEME IN THE
RP OXYGEN-BOUND AND OXYGEN-FREE FORM.
RX PubMed=18980385; DOI=10.1021/bi8012356;
RA Podust L.M., Ioanoviciu A., Ortiz de Montellano P.R.;
RT "2.3 A X-ray structure of the heme-bound GAF domain of sensory histidine
RT kinase DosT of Mycobacterium tuberculosis.";
RL Biochemistry 47:12523-12531(2008).
RN [14] {ECO:0007744|PDB:3ZXQ}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 451-573, AND DOMAIN.
RC STRAIN=H37Rv;
RX PubMed=23486471; DOI=10.1074/jbc.m112.442467;
RA Cho H.Y., Lee Y.H., Bae Y.S., Kim E., Kang B.S.;
RT "Activation of ATP binding for the autophosphorylation of DosS, a
RT Mycobacterium tuberculosis histidine kinase lacking an ATP lid motif.";
RL J. Biol. Chem. 288:12437-12447(2013).
CC -!- FUNCTION: Interacts with the two-component regulatory system DevR/DevS
CC (DosR/DosS) involved in onset of the dormancy response. Required for
CC full induction of the DevR (DosR) regulon; required during early
CC adaptation to anaerobiosis, to start induction of the DevR regulon
CC (PubMed:19487478). May act as a direct hypoxia/oxygen sensor
CC (PubMed:17609369, PubMed:17600145, PubMed:28977726). O(2) acts as a
CC switch, with the Fe(2+)-O(2)-bound protein inactive in
CC autophosphorylation (PubMed:17600145). Autophosphorylates under
CC anaerobic but not aerobic conditions, binding of NO or CO has no effect
CC on autophosphorylation (PubMed:17600145). Binds a number of gases;
CC O(2), NO, CO (PubMed:17609369, PubMed:17600145). May be a secondary
CC sensor for CO (PubMed:18400743). Donates a phosphate group to
CC transcriptional regulator DevR (DosR) (PubMed:15135056,
CC PubMed:15033981, PubMed:28977726). {ECO:0000269|PubMed:15033981,
CC ECO:0000269|PubMed:15135056, ECO:0000269|PubMed:17600145,
CC ECO:0000269|PubMed:17609369, ECO:0000269|PubMed:18400743,
CC ECO:0000269|PubMed:18474359, ECO:0000269|PubMed:19487478,
CC ECO:0000269|PubMed:28977726}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + protein L-histidine = ADP + protein N-phospho-L-
CC histidine.; EC=2.7.13.3; Evidence={ECO:0000269|PubMed:15033981};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15135056, ECO:0000269|PubMed:17600145,
CC ECO:0000269|PubMed:28977726};
CC Note=Mg(2+). Both Mn(2+) and Ca(2+) can substitute Mg(2+) ion in the
CC autophosphorylation reaction but not for phosphate transfer to DevR
CC (DosR) (PubMed:15135056). In another study Mn(2+) and Ca(2+) substitute
CC poorly for autophosphorylation (PubMed:17600145). In another study
CC Mg(2+) or Mn(2+) are required for transfer, but Ca(2+) does not
CC substitute as well (PubMed:28977726). {ECO:0000269|PubMed:15135056,
CC ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:28977726};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:15135056, ECO:0000269|PubMed:17600145,
CC ECO:0000269|PubMed:18980385};
CC Note=Binds 1 heme group per monomer (PubMed:15135056, PubMed:17600145,
CC PubMed:18980385). Half-life of Fe(2+) DosT is over 60 hours in air
CC (PubMed:17600145). {ECO:0000269|PubMed:15135056,
CC ECO:0000269|PubMed:17600145, ECO:0000269|PubMed:18980385};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for ATP for autophosphorylation by deoxy-DosT
CC {ECO:0000269|PubMed:17600145};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:17600145}.
CC -!- INDUCTION: Expressed during aerobic growth, it is not further induced
CC in hypoxia, or by nitric oxide (NO) or carbon monoxide (CO) treatment
CC (PubMed:15135056, PubMed:19487478). Expression is not changed in a devR
CC deletion mutant; i.e. it is not part of the dormancy regulon
CC (PubMed:19487478). {ECO:0000269|PubMed:15135056,
CC ECO:0000269|PubMed:19487478}.
CC -!- DOMAIN: The isolated ATP-binding domain (residues 451-573) crystallized
CC as an asymmetric, domain-swapped dimer without ATP (PubMed:23486471).
CC {ECO:0000269|PubMed:23486471}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene show no changes in gene
CC induction following hypoxia, or exposure to NO or CO (PubMed:18474359).
CC Another publication shows a slightly reduced response to CO
CC (PubMed:18400743). Cells lacking both this gene and DevS (DosS) have no
CC response to hypoxia, or exposure to NO or CO showing both proteins are
CC required for the hypoxic, NO and CO responses (PubMed:15033981). 30%
CC decreased induction of the DevR (DosR) regulon during anaerobic growth,
CC 50% decreased induction of the DevR regulon upon exposure to NO during
CC aerobic growth (PubMed:19487478). {ECO:0000269|PubMed:15033981,
CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359,
CC ECO:0000269|PubMed:19487478}.
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DR EMBL; AL123456; CCP44800.1; -; Genomic_DNA.
DR PIR; B70942; B70942.
DR RefSeq; NP_216543.1; NC_000962.3.
DR RefSeq; WP_003899138.1; NZ_NVQJ01000046.1.
DR PDB; 2VZW; X-ray; 2.30 A; A/B=61-208.
DR PDB; 3ZXQ; X-ray; 1.90 A; A/B=451-573.
DR PDBsum; 2VZW; -.
DR PDBsum; 3ZXQ; -.
DR AlphaFoldDB; P9WGK1; -.
DR SMR; P9WGK1; -.
DR STRING; 83332.Rv2027c; -.
DR iPTMnet; P9WGK1; -.
DR PaxDb; P9WGK1; -.
DR GeneID; 888471; -.
DR KEGG; mtu:Rv2027c; -.
DR TubercuList; Rv2027c; -.
DR eggNOG; COG2203; Bacteria.
DR eggNOG; COG4585; Bacteria.
DR OMA; NCKKHAG; -.
DR PhylomeDB; P9WGK1; -.
DR BRENDA; 2.7.13.3; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR GO; GO:0005509; F:calcium ion binding; IDA:MTBBASE.
DR GO; GO:0070025; F:carbon monoxide binding; IDA:MTBBASE.
DR GO; GO:0020037; F:heme binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0070026; F:nitric oxide binding; IDA:MTBBASE.
DR GO; GO:0019825; F:oxygen binding; IDA:MTBBASE.
DR GO; GO:0019826; F:oxygen sensor activity; IDA:MTBBASE.
DR GO; GO:0000155; F:phosphorelay sensor kinase activity; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0004673; F:protein histidine kinase activity; IDA:MTBBASE.
DR GO; GO:0004672; F:protein kinase activity; IDA:MTBBASE.
DR GO; GO:0070483; P:detection of hypoxia; IDA:MTBBASE.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MTBBASE.
DR Gene3D; 3.30.450.40; -; 2.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR003018; GAF.
DR InterPro; IPR029016; GAF-like_dom_sf.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR011712; Sig_transdc_His_kin_sub3_dim/P.
DR Pfam; PF13185; GAF_2; 1.
DR Pfam; PF13492; GAF_3; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF07730; HisKA_3; 1.
DR SMART; SM00065; GAF; 2.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Heme; Iron; Kinase; Magnesium; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transferase;
KW Two-component regulatory system.
FT CHAIN 1..573
FT /note="Oxygen sensor histidine kinase response regulator
FT DosT"
FT /id="PRO_0000392624"
FT DOMAIN 61..198
FT /note="GAF 1"
FT DOMAIN 229..366
FT /note="GAF 2"
FT DOMAIN 380..573
FT /note="Histidine kinase"
FT /evidence="ECO:0000305"
FT REGION 451..573
FT /note="ATP-binding domain"
FT /evidence="ECO:0000305|PubMed:23486471"
FT BINDING 147
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:18980385"
FT MOD_RES 392
FT /note="Phosphohistidine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:15135056"
FT MUTAGEN 85
FT /note="G->E: Heme iron oxidizes more easily."
FT /evidence="ECO:0000269|PubMed:21536032"
FT MUTAGEN 392..394
FT /note="HDH->KDK: No autophosphorylation, no phosphate
FT transfer to DevR (DosR)."
FT MUTAGEN 392
FT /note="H->Q: No autophosphorylation."
FT /evidence="ECO:0000269|PubMed:15135056"
FT HELIX 62..77
FT /evidence="ECO:0007829|PDB:2VZW"
FT STRAND 79..87
FT /evidence="ECO:0007829|PDB:2VZW"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:2VZW"
FT HELIX 103..109
FT /evidence="ECO:0007829|PDB:2VZW"
FT HELIX 118..124
FT /evidence="ECO:0007829|PDB:2VZW"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:2VZW"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:2VZW"
FT STRAND 153..160
FT /evidence="ECO:0007829|PDB:2VZW"
FT STRAND 163..174
FT /evidence="ECO:0007829|PDB:2VZW"
FT HELIX 181..200
FT /evidence="ECO:0007829|PDB:2VZW"
FT HELIX 453..464
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT STRAND 469..477
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT HELIX 484..502
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT STRAND 509..526
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT HELIX 533..535
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT HELIX 537..550
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT STRAND 553..558
FT /evidence="ECO:0007829|PDB:3ZXQ"
FT STRAND 562..571
FT /evidence="ECO:0007829|PDB:3ZXQ"
SQ SEQUENCE 573 AA; 62169 MW; 83875E7C555D156E CRC64;
MTHPDRANVN PGSPPLRETL SQLRLRELLL EVQDRIEQIV EGRDRLDGLI DAILAITSGL
KLDATLRAIV HTAAELVDAR YGALGVRGYD HRLVEFVYEG IDEETRHLIG SLPEGRGVLG
ALIEEPKPIR LDDISRHPAS VGFPLHHPPM RTFLGVPVRI RDEVFGNLYL TEKADGQPFS
DDDEVLVQAL AAAAGIAVDN ARLFEESRTR EAWIEATRDI GTQMLAGADP AMVFRLIAEE
ALTLMAGAAT LVAVPLDDEA PACEVDDLVI VEVAGEISPA VKQMTVAVSG TSIGGVFHDR
TPRRFDRLDL AVDGPVEPGP ALVLPLRAAD TVAGVLVALR SADEQPFSDK QLDMMAAFAD
QAALAWRLAT AQRQMREVEI LTDRDRIARD LHDHVIQRLF AVGLTLQGAA PRARVPAVRE
SIYSSIDDLQ EIIQEIRSAI FDLHAGPSRA TGLRHRLDKV IDQLAIPALH TTVQYTGPLS
VVDTVLANHA EAVLREAVSN AVRHANATSL AINVSVEDDV RVEVVDDGVG ISGDITESGL
RNLRQRADDA GGEFTVENMP TGGTLLRWSA PLR
