TPX_MYCTU
ID TPX_MYCTU Reviewed; 165 AA.
AC P9WG35; L0TB06; P66952; P95282;
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=Thiol peroxidase {ECO:0000255|HAMAP-Rule:MF_00269, ECO:0000303|PubMed:14871480};
DE Short=Tpx {ECO:0000255|HAMAP-Rule:MF_00269};
DE EC=1.11.1.24 {ECO:0000255|HAMAP-Rule:MF_00269, ECO:0000269|PubMed:14871480};
DE AltName: Full=Peroxiredoxin tpx {ECO:0000255|HAMAP-Rule:MF_00269};
DE Short=Prx {ECO:0000255|HAMAP-Rule:MF_00269};
DE AltName: Full=Thioredoxin peroxidase {ECO:0000255|HAMAP-Rule:MF_00269};
DE AltName: Full=Thioredoxin-dependent peroxiredoxin {ECO:0000255|HAMAP-Rule:MF_00269};
GN Name=tpx {ECO:0000255|HAMAP-Rule:MF_00269}; OrderedLocusNames=Rv1932;
GN ORFNames=MTCY09F9.32c;
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, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14871480; DOI=10.1016/j.abb.2003.11.021;
RA Jaeger T., Budde H., Flohe L., Menge U., Singh M., Trujillo M., Radi R.;
RT "Multiple thioredoxin-mediated routes to detoxify hydroperoxides in
RT Mycobacterium tuberculosis.";
RL Arch. Biochem. Biophys. 423:182-191(2004).
RN [3]
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 [4]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 3-165.
RX PubMed=16627951; DOI=10.1107/s0907444906008249;
RA Stehr M., Hecht H.J., Jaeger T., Flohe L., Singh M.;
RT "Structure of the inactive variant C60S of Mycobacterium tuberculosis thiol
RT peroxidase.";
RL Acta Crystallogr. D 62:563-567(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS), SUBUNIT, AND MUTAGENESIS OF CYS-60;
RP CYS-80 AND CYS-93.
RX PubMed=16884737; DOI=10.1016/j.jmb.2006.05.076;
RA Rho B.S., Hung L.W., Holton J.M., Vigil D., Kim S.I., Park M.S.,
RA Terwilliger T.C., Pedelacq J.D.;
RT "Functional and structural characterization of a thiol peroxidase from
RT Mycobacterium tuberculosis.";
RL J. Mol. Biol. 361:850-863(2006).
CC -!- FUNCTION: Thiol-specific peroxidase that catalyzes the reduction of
CC hydrogen peroxide and organic hydroperoxides to water and alcohols,
CC respectively. Plays a role in cell protection against oxidative stress
CC by detoxifying peroxides. {ECO:0000255|HAMAP-Rule:MF_00269,
CC ECO:0000269|PubMed:14871480}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[thioredoxin]-dithiol + a hydroperoxide = [thioredoxin]-
CC disulfide + an alcohol + H2O; Xref=Rhea:RHEA:62620, Rhea:RHEA-
CC COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924,
CC ChEBI:CHEBI:50058; EC=1.11.1.24; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_00269, ECO:0000269|PubMed:14871480};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=14.5 uM for tert-butyl hydroperoxide (using thioredoxin TrxB as
CC electron donor) {ECO:0000269|PubMed:14871480};
CC KM=184.5 uM for tert-butyl hydroperoxide (using thioredoxin TrxC as
CC electron donor) {ECO:0000269|PubMed:14871480};
CC KM=2.0 uM for TrxB (using tert-butyl hydroperoxide as substrate)
CC {ECO:0000269|PubMed:14871480};
CC KM=120.7 uM for TrxC (using tert-butyl hydroperoxide as substrate)
CC {ECO:0000269|PubMed:14871480};
CC Note=kcat is 0.70 sec(-1) with tert-butyl hydroperoxide as substrate
CC and TrxB as reductant and 11.1 sec(-1) with tert-butyl hydroperoxide
CC as substrate and TrxC as reductant. {ECO:0000269|PubMed:14871480};
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_00269,
CC ECO:0000269|PubMed:16884737}.
CC -!- MISCELLANEOUS: The active site is a conserved redox-active cysteine
CC residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic
CC attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to
CC cysteine sulfenic acid (C(P)-SOH), which then reacts with another
CC cysteine residue, the resolving cysteine (C(R)), to form a disulfide
CC bridge. The disulfide is subsequently reduced by an appropriate
CC electron donor to complete the catalytic cycle. In this atypical 2-Cys
CC peroxiredoxin, C(R) is present in the same subunit to form an
CC intramolecular disulfide. The disulfide is subsequently reduced by
CC thioredoxin (TrxB and TrxC). {ECO:0000255|HAMAP-Rule:MF_00269,
CC ECO:0000305|PubMed:14871480}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. Tpx subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_00269}.
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DR EMBL; AL123456; CCP44699.1; -; Genomic_DNA.
DR PIR; H70635; H70635.
DR RefSeq; NP_216448.1; NC_000962.3.
DR RefSeq; WP_003409700.1; NZ_NVQJ01000034.1.
DR PDB; 1XVQ; X-ray; 1.75 A; A=1-165.
DR PDB; 1Y25; X-ray; 2.10 A; A/B=3-165.
DR PDBsum; 1XVQ; -.
DR PDBsum; 1Y25; -.
DR AlphaFoldDB; P9WG35; -.
DR SMR; P9WG35; -.
DR STRING; 83332.Rv1932; -.
DR DrugBank; DB03382; S-oxy-L-cysteine.
DR PaxDb; P9WG35; -.
DR DNASU; 885357; -.
DR GeneID; 885357; -.
DR KEGG; mtu:Rv1932; -.
DR TubercuList; Rv1932; -.
DR eggNOG; COG2077; Bacteria.
DR OMA; ITQEPNY; -.
DR PhylomeDB; P9WG35; -.
DR Reactome; R-HSA-1222538; Tolerance by Mtb to nitric oxide produced by macrophages.
DR Reactome; R-HSA-1222541; Cell redox homeostasis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:UniProtKB.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; IDA:MTBBASE.
DR GO; GO:0004601; F:peroxidase activity; IDA:MTBBASE.
DR GO; GO:0051920; F:peroxiredoxin activity; IDA:MTBBASE.
DR GO; GO:0008379; F:thioredoxin peroxidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0045454; P:cell redox homeostasis; IDA:MTBBASE.
DR GO; GO:0098754; P:detoxification; IDA:MTBBASE.
DR GO; GO:0051409; P:response to nitrosative stress; IDA:MTBBASE.
DR GO; GO:0006979; P:response to oxidative stress; IDA:MTBBASE.
DR CDD; cd03014; PRX_Atyp2cys; 1.
DR HAMAP; MF_00269; Tpx; 1.
DR InterPro; IPR013740; Redoxin.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR InterPro; IPR002065; TPX.
DR InterPro; IPR018219; Tpx_CS.
DR Pfam; PF08534; Redoxin; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
DR PROSITE; PS01265; TPX; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Disulfide bond; Oxidoreductase; Peroxidase;
KW Redox-active center; Reference proteome.
FT CHAIN 1..165
FT /note="Thiol peroxidase"
FT /id="PRO_0000187888"
FT DOMAIN 18..165
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00269"
FT ACT_SITE 60
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000250|UniProtKB:P0A862, ECO:0000255|HAMAP-
FT Rule:MF_00269, ECO:0000305|PubMed:16884737"
FT DISULFID 60..93
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:P0A862, ECO:0000255|HAMAP-
FT Rule:MF_00269, ECO:0000305|PubMed:16884737"
FT MUTAGEN 60
FT /note="C->S: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:16884737"
FT MUTAGEN 80
FT /note="C->S: Increases catalytic activity."
FT /evidence="ECO:0000269|PubMed:16884737"
FT MUTAGEN 93
FT /note="C->S: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:16884737"
FT STRAND 3..6
FT /evidence="ECO:0007829|PDB:1Y25"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1XVQ"
FT HELIX 39..42
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:1XVQ"
FT HELIX 62..73
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 77..84
FT /evidence="ECO:0007829|PDB:1XVQ"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:1XVQ"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:1XVQ"
FT TURN 123..126
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 130..135
FT /evidence="ECO:0007829|PDB:1XVQ"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:1XVQ"
FT HELIX 156..165
FT /evidence="ECO:0007829|PDB:1XVQ"
SQ SEQUENCE 165 AA; 16896 MW; B251D5DADE2286FE CRC64;
MAQITLRGNA INTVGELPAV GSPAPAFTLT GGDLGVISSD QFRGKSVLLN IFPSVDTPVC
ATSVRTFDER AAASGATVLC VSKDLPFAQK RFCGAEGTEN VMPASAFRDS FGEDYGVTIA
DGPMAGLLAR AIVVIGADGN VAYTELVPEI AQEPNYEAAL AALGA
