AHPD_MYCTU
ID AHPD_MYCTU Reviewed; 177 AA.
AC P9WQB5; L0T9S9; P0A5N4; Q57353;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 38.
DE RecName: Full=Alkyl hydroperoxide reductase AhpD {ECO:0000255|HAMAP-Rule:MF_01676};
DE EC=1.11.1.28 {ECO:0000255|HAMAP-Rule:MF_01676};
DE AltName: Full=Alkylhydroperoxidase AhpD {ECO:0000255|HAMAP-Rule:MF_01676};
GN Name=ahpD {ECO:0000255|HAMAP-Rule:MF_01676}; OrderedLocusNames=Rv2429;
GN ORFNames=MTCY428.17c;
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 [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RA Zhang Y., Dhandayuthapani S., Deretic V.;
RL Submitted (JAN-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
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 [3]
RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-130 AND CYS-133.
RX PubMed=10766746; DOI=10.1074/jbc.m001001200;
RA Hillas P.J., del Alba F.S., Oyarzabal J., Wilks A.,
RA Ortiz De Montellano P.R.;
RT "The AhpC and AhpD antioxidant defense system of Mycobacterium
RT tuberculosis.";
RL J. Biol. Chem. 275:18801-18809(2000).
RN [4]
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=15178486; DOI=10.1016/j.abb.2004.04.017;
RA Koshkin A., Knudsen G.M., Ortiz De Montellano P.R.;
RT "Intermolecular interactions in the AhpC/AhpD antioxidant defense system of
RT Mycobacterium tuberculosis.";
RL Arch. Biochem. Biophys. 427:41-47(2004).
RN [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), ACTIVE SITE, AND SUBUNIT.
RX PubMed=11914371; DOI=10.1074/jbc.m200864200;
RA Nunn C.M., Djordjevic S., Hillas P.J., Nishida C.R.,
RA Ortiz de Montellano P.R.;
RT "The crystal structure of Mycobacterium tuberculosis alkylhydroperoxidase
RT AhpD, a potential target for antitubercular drug design.";
RL J. Biol. Chem. 277:20033-20040(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), FUNCTION, SUBUNIT, AND MUTAGENESIS
RP OF CYS-130 AND CYS-133.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11799204; DOI=10.1126/science.1067798;
RA Bryk R., Lima C.D., Erdjument-Bromage H., Tempst P., Nathan C.;
RT "Metabolic enzymes of mycobacteria linked to antioxidant defense by a
RT thioredoxin-like protein.";
RL Science 295:1073-1077(2002).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF MUTANTS GLN-132 AND PHE-137,
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF GLU-118;
RP CYS-130; HIS-132; CYS-133 AND HIS-137.
RX PubMed=12761216; DOI=10.1074/jbc.m303747200;
RA Koshkin A., Nunn C.M., Djordjevic S., Ortiz de Montellano P.R.;
RT "The mechanism of Mycobacterium tuberculosis alkylhydroperoxidase AhpD as
RT defined by mutagenesis, crystallography, and kinetics.";
RL J. Biol. Chem. 278:29502-29508(2003).
CC -!- FUNCTION: Antioxidant protein with alkyl hydroperoxidase activity.
CC Required for the reduction of the AhpC active site cysteine residues
CC and for the regeneration of the AhpC enzyme activity.
CC -!- FUNCTION: Together with AhpC, DlaT and Lpd, constitutes an NADH-
CC dependent peroxidase active against hydrogen and alkyl peroxides as
CC well as serving as a peroxynitrite reductase, thus protecting the
CC bacterium against reactive nitrogen intermediates and oxidative stress
CC generated by the host immune system.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-N(6)-dihydrolipoyl-L-lysyl-[lipoyl-carrier protein] + a
CC hydroperoxide = (R)-N(6)-lipoyl-L-lysyl-[lipoyl-carrier protein] + an
CC alcohol + H2O; Xref=Rhea:RHEA:62636, Rhea:RHEA-COMP:10502, Rhea:RHEA-
CC COMP:16355, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879, ChEBI:CHEBI:35924,
CC ChEBI:CHEBI:83099, ChEBI:CHEBI:83100; EC=1.11.1.28;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01676};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.2. {ECO:0000269|PubMed:12761216};
CC -!- SUBUNIT: Homotrimer. Identified in a complex with AhpC, DlaT and Lpd.
CC {ECO:0000255|HAMAP-Rule:MF_01676, ECO:0000269|PubMed:10766746,
CC ECO:0000269|PubMed:11799204, ECO:0000269|PubMed:11914371,
CC ECO:0000269|PubMed:15178486}.
CC -!- SIMILARITY: Belongs to the AhpD family. {ECO:0000255|HAMAP-
CC Rule:MF_01676}.
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; U44840; AAA86657.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45221.1; -; Genomic_DNA.
DR PIR; C70679; C70679.
DR RefSeq; NP_216945.1; NC_000962.3.
DR RefSeq; WP_003412536.1; NZ_NVQJ01000024.1.
DR PDB; 1GU9; X-ray; 1.90 A; A/B/C/D/E/F/G/H/I/J/K/L=1-177.
DR PDB; 1KNC; X-ray; 2.00 A; A/B/C=1-177.
DR PDB; 1LW1; X-ray; 2.30 A; A/B/C=1-177.
DR PDB; 1ME5; X-ray; 2.40 A; A/B/C=1-177.
DR PDBsum; 1GU9; -.
DR PDBsum; 1KNC; -.
DR PDBsum; 1LW1; -.
DR PDBsum; 1ME5; -.
DR AlphaFoldDB; P9WQB5; -.
DR SMR; P9WQB5; -.
DR STRING; 83332.Rv2429; -.
DR PaxDb; P9WQB5; -.
DR DNASU; 885959; -.
DR GeneID; 45426419; -.
DR GeneID; 885959; -.
DR KEGG; mtu:Rv2429; -.
DR TubercuList; Rv2429; -.
DR eggNOG; COG0599; Bacteria.
DR OMA; AIMAMNN; -.
DR PhylomeDB; P9WQB5; -.
DR BRENDA; 1.11.1.28; 3445.
DR Reactome; R-HSA-1222541; Cell redox homeostasis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008785; F:alkyl hydroperoxide reductase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; IDA:MTBBASE.
DR GO; GO:0032843; F:hydroperoxide reductase activity; IDA:MTBBASE.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0004601; F:peroxidase activity; IEA:UniProtKB-KW.
DR GO; GO:0051920; F:peroxiredoxin activity; IEA:InterPro.
DR GO; GO:0045454; P:cell redox homeostasis; IPI:MTBBASE.
DR GO; GO:0006979; P:response to oxidative stress; IEA:InterPro.
DR Gene3D; 1.20.1290.10; -; 1.
DR HAMAP; MF_01676; AhpD; 1.
DR InterPro; IPR004674; AhpD.
DR InterPro; IPR029032; AhpD-like.
DR InterPro; IPR004675; AhpD_core.
DR InterPro; IPR003779; CMD-like.
DR Pfam; PF02627; CMD; 1.
DR SUPFAM; SSF69118; SSF69118; 1.
DR TIGRFAMs; TIGR00777; ahpD; 1.
DR TIGRFAMs; TIGR00778; ahpD_dom; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antioxidant; Disulfide bond; Oxidoreductase; Peroxidase;
KW Redox-active center; Reference proteome.
FT CHAIN 1..177
FT /note="Alkyl hydroperoxide reductase AhpD"
FT /id="PRO_0000064507"
FT ACT_SITE 130
FT /note="Proton donor"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01676,
FT ECO:0000269|PubMed:11914371"
FT ACT_SITE 133
FT /note="Cysteine sulfenic acid (-SOH) intermediate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01676,
FT ECO:0000269|PubMed:11914371"
FT DISULFID 130..133
FT /evidence="ECO:0000269|PubMed:15178486"
FT DISULFID 133
FT /note="Interchain (with C-61 in AhpC); in linked form"
FT /evidence="ECO:0000269|PubMed:15178486"
FT MUTAGEN 118
FT /note="E->Q: Reduces protein stability. No effect on
FT catalytic activity."
FT /evidence="ECO:0000269|PubMed:12761216"
FT MUTAGEN 130
FT /note="C->S: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10766746,
FT ECO:0000269|PubMed:11799204, ECO:0000269|PubMed:12761216"
FT MUTAGEN 132
FT /note="H->F: Slightly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12761216"
FT MUTAGEN 132
FT /note="H->Q: Slightly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12761216"
FT MUTAGEN 133
FT /note="C->S: Loss of activity. Loss of interchain disulfide
FT bond with AhpC."
FT /evidence="ECO:0000269|PubMed:10766746,
FT ECO:0000269|PubMed:11799204, ECO:0000269|PubMed:12761216"
FT MUTAGEN 137
FT /note="H->F: Reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12761216"
FT MUTAGEN 137
FT /note="H->Q: Slightly reduced catalytic activity."
FT /evidence="ECO:0000269|PubMed:12761216"
FT HELIX 3..9
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:1KNC"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 32..45
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 49..59
FT /evidence="ECO:0007829|PDB:1KNC"
FT TURN 60..62
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 65..90
FT /evidence="ECO:0007829|PDB:1KNC"
FT TURN 91..97
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 114..128
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 131..143
FT /evidence="ECO:0007829|PDB:1KNC"
FT HELIX 148..173
FT /evidence="ECO:0007829|PDB:1KNC"
SQ SEQUENCE 177 AA; 18781 MW; B7DD28AA9BD9B24C CRC64;
MSIEKLKAAL PEYAKDIKLN LSSITRSSVL DQEQLWGTLL ASAAATRNPQ VLADIGAEAT
DHLSAAARHA ALGAAAIMGM NNVFYRGRGF LEGRYDDLRP GLRMNIIANP GIPKANFELW
SFAVSAINGC SHCLVAHEHT LRTVGVDREA IFEALKAAAI VSGVAQALAT IEALSPS
