AHPE_MYCTU
ID AHPE_MYCTU Reviewed; 153 AA.
AC P9WIE3; L0TAL3; P65688; Q10520;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 49.
DE RecName: Full=Alkyl hydroperoxide reductase E;
DE EC=1.11.1.29 {ECO:0000269|PubMed:19737009};
DE AltName: Full=Mycoredoxin-dependent peroxiredoxin {ECO:0000305};
DE AltName: Full=Peroxiredoxin AhpE;
DE Short=Prx;
DE AltName: Full=Thioredoxin peroxidase;
DE Short=TPx;
GN Name=ahpE; OrderedLocusNames=Rv2238c; ORFNames=MTCY427.19c;
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, ACTIVE SITE, AND SUBUNIT.
RX PubMed=19737009; DOI=10.1021/bi901221s;
RA Hugo M., Turell L., Manta B., Botti H., Monteiro G., Netto L.E.,
RA Alvarez B., Radi R., Trujillo M.;
RT "Thiol and sulfenic acid oxidation of AhpE, the one-cysteine peroxiredoxin
RT from Mycobacterium tuberculosis: kinetics, acidity constants, and
RT conformational dynamics.";
RL Biochemistry 48:9416-9426(2009).
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 FUNCTION.
RX PubMed=24379404; DOI=10.1074/jbc.m113.510248;
RA Hugo M., Van Laer K., Reyes A.M., Vertommen D., Messens J., Radi R.,
RA Trujillo M.;
RT "Mycothiol/mycoredoxin 1-dependent reduction of the peroxiredoxin AhpE from
RT Mycobacterium tuberculosis.";
RL J. Biol. Chem. 289:5228-5239(2014).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), AND ACTIVE SITE.
RX PubMed=15701515; DOI=10.1016/j.jmb.2004.12.046;
RA Li S., Peterson N.A., Kim M.Y., Kim C.Y., Hung L.W., Yu M., Lekin T.,
RA Segelke B.W., Lott J.S., Baker E.N.;
RT "Crystal Structure of AhpE from Mycobacterium tuberculosis, a 1-Cys
RT peroxiredoxin.";
RL J. Mol. Biol. 346:1035-1046(2005).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 1-152.
RX PubMed=27471753; DOI=10.1039/c6cc02645a;
RA Pedre B., van Bergen L.A., Pallo A., Rosado L.A., Dufe V.T., Molle I.V.,
RA Wahni K., Erdogan H., Alonso M., Proft F.D., Messens J.;
RT "The active site architecture in peroxiredoxins: a case study on
RT Mycobacterium tuberculosis AhpE.";
RL Chem. Commun. (Camb.) 52:10293-10296(2016).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS), AND SUBUNIT.
RX PubMed=27417938; DOI=10.1016/j.freeradbiomed.2016.07.007;
RA Kumar A., Balakrishna A.M., Nartey W., Manimekalai M.S., Grueber G.;
RT "Redox chemistry of Mycobacterium tuberculosis alkylhydroperoxide reductase
RT E (AhpE): Structural and mechanistic insight into a mycoredoxin-1
RT independent reductive pathway of AhpE via mycothiol.";
RL Free Radic. Biol. Med. 97:588-601(2016).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.87 ANGSTROMS) OF 1-152.
RX PubMed=27468924; DOI=10.1038/srep30369;
RA van Bergen L.A., Alonso M., Pallo A., Nilsson L., De Proft F., Messens J.;
RT "Revisiting sulfur H-bonds in proteins: The example of peroxiredoxin
RT AhpE.";
RL Sci. Rep. 6:30369-30369(2016).
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. May represent an important antioxidant
CC defense against cytotoxic peroxides, especially peroxynitrite, which
CC can be formed by activated macrophages during infection.
CC {ECO:0000269|PubMed:19737009, ECO:0000269|PubMed:24379404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[mycoredoxin]-L-dithiol + a hydroperoxide = [mycoredoxin]-L-
CC disulfide + an alcohol + H2O; Xref=Rhea:RHEA:62640, Rhea:RHEA-
CC COMP:16137, Rhea:RHEA-COMP:16138, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924,
CC ChEBI:CHEBI:50058; EC=1.11.1.29;
CC Evidence={ECO:0000269|PubMed:19737009};
CC -!- SUBUNIT: Homodimer (PubMed:19737009, PubMed:27417938). Forms both
CC dimers and octamers; a tightly-associated dimer and a ring-like octamer
CC (PubMed:15701515). {ECO:0000269|PubMed:15701515,
CC ECO:0000269|PubMed:19737009, ECO:0000269|PubMed:27417938}.
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 1-Cys
CC peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide
CC with a cysteine from another protein or with a small thiol molecule.
CC C(P) can be reduced through a mixed disulfide with the N-terminal
CC cysteine of mycoredoxin-1 (Mrx1), resolved by its C-terminal cysteine,
CC or by a mixed disulfide with mycothiol, resolved by a second molecule
CC of mycothiol or by mycoredoxin-1. {ECO:0000305|PubMed:24379404,
CC ECO:0000305|PubMed:27417938}.
CC -!- SIMILARITY: Belongs to the peroxiredoxin family. AhpE subfamily.
CC {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; CCP45018.1; -; Genomic_DNA.
DR PIR; B70778; B70778.
DR RefSeq; NP_216754.1; NC_000962.3.
DR RefSeq; WP_003411527.1; NZ_NVQJ01000008.1.
DR PDB; 1XVW; X-ray; 1.90 A; A/B=1-153.
DR PDB; 1XXU; X-ray; 1.90 A; A/B/C/D=1-153.
DR PDB; 4X0X; X-ray; 1.90 A; A/B/C/D=1-153.
DR PDB; 4X1U; X-ray; 1.87 A; A/B=1-152.
DR PDB; 4XIH; X-ray; 2.25 A; A/B=1-152.
DR PDB; 5C04; X-ray; 1.45 A; A/B=1-152.
DR PDB; 5ID2; X-ray; 2.43 A; A/B/C/D=1-153.
DR PDBsum; 1XVW; -.
DR PDBsum; 1XXU; -.
DR PDBsum; 4X0X; -.
DR PDBsum; 4X1U; -.
DR PDBsum; 4XIH; -.
DR PDBsum; 5C04; -.
DR PDBsum; 5ID2; -.
DR AlphaFoldDB; P9WIE3; -.
DR SMR; P9WIE3; -.
DR STRING; 83332.Rv2238c; -.
DR PaxDb; P9WIE3; -.
DR GeneID; 45426218; -.
DR GeneID; 887871; -.
DR KEGG; mtu:Rv2238c; -.
DR TubercuList; Rv2238c; -.
DR eggNOG; COG1225; Bacteria.
DR OMA; VCTKELC; -.
DR PhylomeDB; P9WIE3; -.
DR BRENDA; 1.11.1.29; 3445.
DR Reactome; R-HSA-1222538; Tolerance by Mtb to nitric oxide produced by macrophages.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
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; IBA:GO_Central.
DR GO; GO:0045454; P:cell redox homeostasis; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0051409; P:response to nitrosative stress; IDA:MTBBASE.
DR InterPro; IPR000866; AhpC/TSA.
DR InterPro; IPR024706; Peroxiredoxin_AhpC-typ.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR013766; Thioredoxin_domain.
DR Pfam; PF00578; AhpC-TSA; 1.
DR PIRSF; PIRSF000239; AHPC; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Oxidoreductase; Peroxidase; Redox-active center;
KW Reference proteome.
FT CHAIN 1..153
FT /note="Alkyl hydroperoxide reductase E"
FT /id="PRO_0000135148"
FT DOMAIN 2..153
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT ACT_SITE 45
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000269|PubMed:15701515,
FT ECO:0000305|PubMed:19737009, ECO:0007744|PDB:1XVW"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 20..23
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:5C04"
FT TURN 27..29
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 60..71
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 74..84
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 90..92
FT /evidence="ECO:0007829|PDB:5C04"
FT TURN 94..98
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:5C04"
FT TURN 109..112
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 116..121
FT /evidence="ECO:0007829|PDB:5C04"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:5C04"
FT HELIX 142..149
FT /evidence="ECO:0007829|PDB:5C04"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:5ID2"
SQ SEQUENCE 153 AA; 16819 MW; B24927599A0A80E2 CRC64;
MLNVGATAPD FTLRDQNQQL VTLRGYRGAK NVLLVFFPLA FTGICQGELD QLRDHLPEFE
NDDSAALAIS VGPPPTHKIW ATQSGFTFPL LSDFWPHGAV SQAYGVFNEQ AGIANRGTFV
VDRSGIIRFA EMKQPGEVRD QRLWTDALAA LTA
