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Protein

Arylamine N-acetyltransferase

Gene

nat

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

Functioni

Catalyzes the transfer of the acetyl group from acetyl coenzyme A to the free amino group of arylamines and hydrazines (PubMed:18795795). Is able to utilize not only acetyl-CoA, but also n-propionyl-CoA and acetoacetyl-CoA as acyl donors, although at a lower rate (PubMed:19014350). As acetyl-CoA and propionyl-CoA are products of cholesterol catabolism and the nat gene is likely present in the same operon than genes involved in cholesterol degradation, this enzyme could have a role in the utilization and regulation of these CoA species (PubMed:19014350).2 Publications
It has been reported that overexpression of this enzyme may be responsible for increased resistance to the front-line antitubercular drug isoniazid (INH), by acetylating and hence inactivating the prodrug (PubMed:9973365). However, isoniazid is an extremely poor substrate for the enzyme; therefore, the expression of TBNAT is unlikely to be a significant cause of isoniazid resistance in M.tuberculosis (PubMed:18795795).2 Publications

Catalytic activityi

Acetyl-CoA + an arylamine = CoA + an N-acetylarylamine.2 Publications

Kineticsi

kcat is 94 sec(-1) with 3-amino-4-hydroxybenzoic acid as substrate. kcat is 66 sec(-1) with 4-amino-3-hydroxybenzoic acid as substrate. kcat is 44 sec(-1) with hydralazine as substrate. kcat is 70 sec(-1) with 2-amino-4-methylphenol as substrate. kcat is 21 sec(-1) with 2-amino-4-chlorophenol as substrate. kcat is 51 sec(-1) with 2-aminophenol as substrate. kcat is 10.9 sec(-1) with 4-hydroxybenzhydrazide as substrate. kcat is 2.9 sec(-1) with anisidine as substrate. kcat is 0.7 sec(-1) with p-aminobenzoic acid as substrate. kcat is 1.9 sec(-1) with benzoic acid hydrazide as substrate. kcat is 0.8 sec(-1) with 4-methylaniline as substrate. kcat is 4.9 sec(-1) with isoniazid as substrate. kcat is 0.6 sec(-1) with nicotinic acid hydrazide as substrate. kcat is 0.2 sec(-1) with 4-chloroaniline as substrate. kcat is 0.28 sec(-1) with aniline as substrate. kcat is 0.9 sec(-1) with 4-fluoroaniline as substrate.1 Publication

  1. KM=0.14 mM for acetyl-CoA1 Publication
  2. KM=0.56 mM for acetyl-CoA1 Publication
  3. KM=0.29 mM for n-propionyl-CoA1 Publication
  4. KM=0.32 mM for 3-amino-4-hydroxybenzoic acid1 Publication
  5. KM=0.90 mM for 4-amino-3-hydroxybenzoic acid1 Publication
  6. KM=0.61 mM for hydralazine1 Publication
  7. KM=3.06 mM for 2-amino-4-methylphenol1 Publication
  8. KM=1.9 mM for 2-amino-4-chlorophenol1 Publication
  9. KM=5.79 mM for 2-aminophenol1 Publication
  10. KM=20 mM for 4-hydroxybenzhydrazide1 Publication
  11. KM=14 mM for anisidine1 Publication
  12. KM=5.0 mM for p-aminobenzoic acid1 Publication
  13. KM=14 mM for benzoic acid hydrazide1 Publication
  14. KM=11 mM for 4-methylaniline1 Publication
  15. KM=102 mM for isoniazid1 Publication
  16. KM=14 mM for nicotinic acid hydrazide1 Publication
  17. KM=6 mM for 4-chloroaniline1 Publication
  18. KM=23 mM for aniline1 Publication
  19. KM=51 mM for 4-fluoroaniline1 Publication

    Temperature dependencei

    Is thermostable. Retains >95% of its activity after incubation at 60 degrees Celsius for 30 minutes.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei70 – 701Acyl-thioester intermediate1 Publication
    Active sitei110 – 1101Proton acceptor1 Publication
    Active sitei127 – 12711 Publication

    GO - Molecular functioni

    • arylamine N-acetyltransferase activity Source: MTBBASE

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Acyltransferase, Transferase

    Keywords - Biological processi

    Antibiotic resistance

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Arylamine N-acetyltransferase1 Publication (EC:2.3.1.52 Publications)
    Short name:
    NAT1 Publication
    Alternative name(s):
    TBNAT2 Publications
    Gene namesi
    Name:nat1 Publication
    Synonyms:nhoA, tbnat
    Ordered Locus Names:Rv3566c
    ORF Names:MTCY06G11.13c
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv3566c.

    Subcellular locationi

    GO - Cellular componenti

    • plasma membrane Source: MTBBASE
    Complete GO annotation...

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 283283Arylamine N-acetyltransferasePRO_0000107919Add
    BLAST

    Proteomic databases

    PaxDbiP9WJI5.

    Interactioni

    Subunit structurei

    Homodimer and homotetramer.By similarity

    Protein-protein interaction databases

    STRINGi83332.Rv3566c.

    Structurei

    3D structure databases

    ProteinModelPortaliP9WJI5.
    SMRiP9WJI5. Positions 3-272.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4108MUX. Bacteria.
    COG2162. LUCA.
    KOiK00622.
    OMAiPFENFDI.
    PhylomeDBiP9WJI5.

    Family and domain databases

    InterProiIPR001447. Arylamine_N-AcTrfase.
    [Graphical view]
    PANTHERiPTHR11786. PTHR11786. 1 hit.
    PfamiPF00797. Acetyltransf_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P9WJI5-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MALDLTAYFD RINYRGATDP TLDVLQDLVT VHSRTIPFEN LDPLLGVPVD
    60 70 80 90 100
    DLSPQALADK LVLRRRGGYC FEHNGLMGYV LAELGYRVRR FAARVVWKLA
    110 120 130 140 150
    PDAPLPPQTH TLLGVTFPGS GGCYLVDVGF GGQTPTSPLR LETGAVQPTT
    160 170 180 190 200
    HEPYRLEDRV DGFVLQAMVR DTWQTLYEFT TQTRPQIDLK VASWYASTHP
    210 220 230 240 250
    ASKFVTGLTA AVITDDARWN LSGRDLAVHR AGGTEKIRLA DAAAVVDTLS
    260 270 280
    ERFGINVADI GERGALETRI DELLARQPGA DAP
    Length:283
    Mass (Da):31,029
    Last modified:April 16, 2014 - v1
    Checksum:i9C8D98E3256D088A
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46388.1.
    RefSeqiWP_003419364.1. NZ_KK339374.1.
    YP_177989.1. NC_000962.3.

    Genome annotation databases

    EnsemblBacteriaiCCP46388; CCP46388; Rv3566c.
    GeneIDi888005.
    KEGGimtu:Rv3566c.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46388.1.
    RefSeqiWP_003419364.1. NZ_KK339374.1.
    YP_177989.1. NC_000962.3.

    3D structure databases

    ProteinModelPortaliP9WJI5.
    SMRiP9WJI5. Positions 3-272.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv3566c.

    Proteomic databases

    PaxDbiP9WJI5.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP46388; CCP46388; Rv3566c.
    GeneIDi888005.
    KEGGimtu:Rv3566c.

    Organism-specific databases

    TubercuListiRv3566c.

    Phylogenomic databases

    eggNOGiENOG4108MUX. Bacteria.
    COG2162. LUCA.
    KOiK00622.
    OMAiPFENFDI.
    PhylomeDBiP9WJI5.

    Family and domain databases

    InterProiIPR001447. Arylamine_N-AcTrfase.
    [Graphical view]
    PANTHERiPTHR11786. PTHR11786. 1 hit.
    PfamiPF00797. Acetyltransf_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiNAT_MYCTU
    AccessioniPrimary (citable) accession number: P9WJI5
    Secondary accession number(s): L0TCY1, P0A5L8, P96848
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: July 6, 2016
    This is version 17 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    Was identified as a high-confidence drug target.1 Publication
    Reactions proceed via a bi-bi ping-pong kinetic mechanism.1 Publication
    Resistance to the antitubercular drug isoniazid (INH) has been associated to mutations in this gene in some INH-resistant clinical isolates of M.tuberculosis.1 Publication

    Keywords - Technical termi

    Complete proteome, 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. 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.