Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Alkyl hydroperoxide reductase subunit C

Gene

ahpC

Organism
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Together with AhpD, DlaT and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system. Does not however seem to play a role in detoxification of isoniazid.3 Publications

Catalytic activityi

2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.

Kineticsi

  1. KM=5.38 mM for t-butyl hydroperoxide1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei61Cysteine sulfenic acid (-SOH) intermediate3 Publications1

    GO - Molecular functioni

    • alkyl hydroperoxide reductase activity Source: MTBBASE
    • hydroperoxide reductase activity Source: MTBBASE
    • oxidoreductase activity Source: MTBBASE
    • peroxidase activity Source: MTBBASE
    • peroxiredoxin activity Source: MTBBASE

    GO - Biological processi

    • cell redox homeostasis Source: MTBBASE
    • evasion or tolerance by symbiont of host-produced nitric oxide Source: Reactome
    • evasion or tolerance by symbiont of host-produced reactive oxygen species Source: Reactome
    • oxidation-reduction process Source: MTBBASE
    • response to nitrosative stress Source: MTBBASE
    Complete GO annotation...

    Keywords - Molecular functioni

    Antioxidant, Oxidoreductase, Peroxidase

    Keywords - Biological processi

    Stress response

    Enzyme and pathway databases

    BioCyciMTBH37RV:G185E-6659-MONOMER.
    ReactomeiR-HSA-1222387. Tolerance of reactive oxygen produced by macrophages.
    R-HSA-1222538. Tolerance by Mtb to nitric oxide produced by macrophages.
    R-HSA-1222541. Cell redox homeostasis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Alkyl hydroperoxide reductase subunit C (EC:1.11.1.15)
    Short name:
    MtAhpC
    Alternative name(s):
    Peroxiredoxin
    Thioredoxin peroxidase
    Gene namesi
    Name:ahpC
    Ordered Locus Names:Rv2428
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv2428.

    Subcellular locationi

    GO - Cellular componenti

    • cell wall Source: MTBBASE
    • cytosol Source: Reactome
    • plasma membrane Source: MTBBASE
    Complete GO annotation...

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi61C → A or S: No enzyme activity. 3 Publications1
    Mutagenesisi174 – 176CAC → AAA: 50% reduction in oxidation activity of dithiothreitol and 60% reduction in oxidation of thiocyanate. 1 Publication3
    Mutagenesisi174C → A: Very poor oxidation activity of dithiothreitol and thiocyanate. 3 Publications1
    Mutagenesisi174C → S in reconstituted in vitro system retains no enzyme activity. 3 Publications1
    Mutagenesisi176C → A: 50% reduction in oxidation activity of dithiothreitol and thiocyanate. 3 Publications1
    Mutagenesisi176C → S: Retains about 10% activity with tert-butylhydroperoxide. In reconstituted in vitro system retains 30% enzyme activity. 3 Publications1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00003929132 – 195Alkyl hydroperoxide reductase subunit CAdd BLAST194

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi61Interchain (with C-174); in linked form2 Publications
    Disulfide bondi174Interchain (with C-61); in linked form2 Publications

    Post-translational modificationi

    The Cys-61-SH group is the primary site of oxidation by H2O2, and the oxidized Cys-61 (probably Cys-SOH) rapidly reacts with Cys-174-SH of the other subunit to form an intermolecular disulfide. This disulfide is subsequently reduced by thioredoxin (Probable).Curated

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    PaxDbiP9WQB7.

    Expressioni

    Inductioni

    Induced in isoniazid (INH)-resistant, KatG-deficient strains as well as in INH-sensitive strains when challenged with the drug. Increased expression in these strains probably compensates for loss of katG activity in detoxification of organic peroxides. A possible member of the dormancy regulon. Induced in response to reduced oxygen tension (hypoxia). It is hoped that this regulon will give insight into the latent, or dormant phase of infection.2 Publications

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked, upon oxidation. It has been shown to form 10-mers. The crystal structure of Ser-176 implies that the reduced protein may form a 10- or 12-mer during the catalytic cycle. Identified in a complex with AhpD, DlaT and Lpd.3 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv2428.

    Structurei

    Secondary structure

    1195
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi14 – 18Combined sources5
    Helixi23 – 25Combined sources3
    Helixi31 – 34Combined sources4
    Beta strandi35 – 39Combined sources5
    Beta strandi47 – 52Combined sources6
    Helixi62 – 70Combined sources9
    Helixi72 – 76Combined sources5
    Turni77 – 79Combined sources3
    Beta strandi80 – 88Combined sources9
    Helixi90 – 99Combined sources10
    Helixi103 – 105Combined sources3
    Beta strandi110 – 112Combined sources3
    Helixi117 – 121Combined sources5
    Beta strandi129 – 131Combined sources3
    Beta strandi133 – 138Combined sources6
    Beta strandi142 – 150Combined sources9
    Helixi158 – 169Combined sources12
    Helixi175 – 177Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BMXX-ray2.40A/B/C1-195[»]
    ProteinModelPortaliP9WQB7.
    SMRiP9WQB7.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini4 – 170ThioredoxinPROSITE-ProRule annotationAdd BLAST167

    Sequence similaritiesi

    Belongs to the AhpC/TSA family.Curated
    Contains 1 thioredoxin domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Redox-active center

    Phylogenomic databases

    eggNOGiENOG4105D3R. Bacteria.
    COG0450. LUCA.
    KOiK03386.
    OMAiTAEVHFA.
    PhylomeDBiP9WQB7.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR000866. AhpC/TSA.
    IPR024706. Peroxiredoxin_AhpC-typ.
    IPR012336. Thioredoxin-like_fold.
    IPR013766. Thioredoxin_domain.
    [Graphical view]
    PfamiPF00578. AhpC-TSA. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000239. AHPC. 1 hit.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P9WQB7-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPLLTIGDQF PAYQLTALIG GDLSKVDAKQ PGDYFTTITS DEHPGKWRVV
    60 70 80 90 100
    FFWPKDFTFV CPTEIAAFSK LNDEFEDRDA QILGVSIDSE FAHFQWRAQH
    110 120 130 140 150
    NDLKTLPFPM LSDIKRELSQ AAGVLNADGV ADRVTFIVDP NNEIQFVSAT
    160 170 180 190
    AGSVGRNVDE VLRVLDALQS DELCACNWRK GDPTLDAGEL LKASA
    Length:195
    Mass (Da):21,566
    Last modified:April 16, 2014 - v1
    Checksum:i011C1014F07C7095
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U18264 Genomic DNA. Translation: AAA79919.1.
    U16243 Genomic DNA. Translation: AAC43585.1.
    AF313459 Genomic DNA. Translation: AAG34172.1.
    AF313460 Genomic DNA. Translation: AAG34173.1.
    AF313461 Genomic DNA. Translation: AAG34174.1.
    AF313462 Genomic DNA. Translation: AAG34175.1.
    AF313463 Genomic DNA. Translation: AAG34176.1.
    AL123456 Genomic DNA. Translation: CCP45220.1.
    RefSeqiNP_216944.1. NC_000962.3.
    WP_003412529.1. NZ_KK339370.1.

    Genome annotation databases

    EnsemblBacteriaiCCP45220; CCP45220; Rv2428.
    GeneIDi885717.
    KEGGimtu:Rv2428.
    mtv:RVBD_2428.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U18264 Genomic DNA. Translation: AAA79919.1.
    U16243 Genomic DNA. Translation: AAC43585.1.
    AF313459 Genomic DNA. Translation: AAG34172.1.
    AF313460 Genomic DNA. Translation: AAG34173.1.
    AF313461 Genomic DNA. Translation: AAG34174.1.
    AF313462 Genomic DNA. Translation: AAG34175.1.
    AF313463 Genomic DNA. Translation: AAG34176.1.
    AL123456 Genomic DNA. Translation: CCP45220.1.
    RefSeqiNP_216944.1. NC_000962.3.
    WP_003412529.1. NZ_KK339370.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    2BMXX-ray2.40A/B/C1-195[»]
    ProteinModelPortaliP9WQB7.
    SMRiP9WQB7.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv2428.

    Proteomic databases

    PaxDbiP9WQB7.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP45220; CCP45220; Rv2428.
    GeneIDi885717.
    KEGGimtu:Rv2428.
    mtv:RVBD_2428.

    Organism-specific databases

    TubercuListiRv2428.

    Phylogenomic databases

    eggNOGiENOG4105D3R. Bacteria.
    COG0450. LUCA.
    KOiK03386.
    OMAiTAEVHFA.
    PhylomeDBiP9WQB7.

    Enzyme and pathway databases

    BioCyciMTBH37RV:G185E-6659-MONOMER.
    ReactomeiR-HSA-1222387. Tolerance of reactive oxygen produced by macrophages.
    R-HSA-1222538. Tolerance by Mtb to nitric oxide produced by macrophages.
    R-HSA-1222541. Cell redox homeostasis.

    Family and domain databases

    Gene3Di3.40.30.10. 1 hit.
    InterProiIPR000866. AhpC/TSA.
    IPR024706. Peroxiredoxin_AhpC-typ.
    IPR012336. Thioredoxin-like_fold.
    IPR013766. Thioredoxin_domain.
    [Graphical view]
    PfamiPF00578. AhpC-TSA. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000239. AHPC. 1 hit.
    SUPFAMiSSF52833. SSF52833. 1 hit.
    PROSITEiPS51352. THIOREDOXIN_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiAHPC_MYCTU
    AccessioniPrimary (citable) accession number: P9WQB7
    Secondary accession number(s): L0T9L3
    , Q79FE2, Q7BHK8, Q7D758
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: November 2, 2016
    This is version 23 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    In the absence of both Cys-174 and Cys-176 the enzyme may adopt a 1-Cys Prx-type mechanism, which would account for the apparent suppression of the Ala-174 mutation by Ala-176.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh
      Mycobacterium tuberculosis strains ATCC 25618 / H37Rv and CDC 1551 / Oshkosh: entries and gene names
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.