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Protein

Homoserine O-succinyltransferase

Gene

metAS

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transfers a succinyl group from succinyl-CoA to L-homoserine, forming succinyl-L-homoserine (PubMed:10572016, PubMed:17442255, PubMed:17302437, Ref. 11). Utilizes a ping-pong kinetic mechanism in which the succinyl group of succinyl-CoA is initially transferred to the enzyme to form a succinyl-enzyme intermediate before subsequent transfer to homoserine to form the final product, O-succinylhomoserine (PubMed:10572016, PubMed:17442255, PubMed:17302437). Cannot use acetyl-CoA (PubMed:10572016).4 Publications

Catalytic activityi

Succinyl-CoA + L-homoserine = CoA + O-succinyl-L-homoserine.UniRule annotation4 Publications

Enzyme regulationi

Inhibited by iodoacetamide in a pH-dependent manner.1 Publication

Kineticsi

kcat is 24 sec(-1) with succinyl-CoA as substrate. kcat is 24 sec(-1) with L-homoserine as substrate. kcat is 5.23 sec(-1) with CoA as substrate. kcat is 5.23 sec(-1) with O-succinylhomoserine as substrate.1 Publication
  1. KM=0.17 mM for succinyl-CoA1 Publication
  2. KM=0.13 mM for succinyl-CoA1 Publication
  3. KM=0.28 mM for succinyl-CoA1 Publication
  4. KM=1.6 mM for L-homoserine1 Publication
  5. KM=0.72 mM for L-homoserine1 Publication
  6. KM=0.38 mM for L-homoserine1 Publication
  7. KM=0.64 mM for CoA1 Publication
  8. KM=3.5 mM for O-succinylhomoserine1 Publication

    Pathwayi: L-methionine biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes O-succinyl-L-homoserine from L-homoserine.UniRule annotation1 Publication
    Proteins known to be involved in this subpathway in this organism are:
    1. Homoserine O-succinyltransferase (metAS)
    This subpathway is part of the pathway L-methionine biosynthesis via de novo pathway, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes O-succinyl-L-homoserine from L-homoserine, the pathway L-methionine biosynthesis via de novo pathway and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei111Important for acyl-CoA specificityUniRule annotation1
    Active sitei142Acyl-thioester intermediateUniRule annotation3 Publications1
    Binding sitei163SubstrateUniRule annotation1
    Binding sitei192SubstrateUniRule annotation1
    Sitei192Important for substrate specificityUniRule annotation1
    Active sitei235Proton acceptorUniRule annotation2 Publications1
    Active sitei237UniRule annotation2 Publications1
    Binding sitei249SubstrateUniRule annotation1

    GO - Molecular functioni

    • homoserine O-succinyltransferase activity Source: EcoCyc

    GO - Biological processi

    Keywordsi

    Molecular functionAcyltransferase, Transferase
    Biological processAmino-acid biosynthesis, Methionine biosynthesis

    Enzyme and pathway databases

    BioCyciEcoCyc:HOMSUCTRAN-MONOMER.
    MetaCyc:HOMSUCTRAN-MONOMER.
    UniPathwayiUPA00051; UER00075.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Homoserine O-succinyltransferase1 PublicationUniRule annotation (EC:2.3.1.46UniRule annotation4 Publications)
    Short name:
    HST1 PublicationUniRule annotation
    Alternative name(s):
    Homoserine transsuccinylase1 PublicationUniRule annotation
    Short name:
    HTS1 PublicationUniRule annotation
    Gene namesi
    Name:metAS1 PublicationUniRule annotation
    Synonyms:metA1 Publication
    Ordered Locus Names:b4013, JW3973
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG10581. metA.

    Subcellular locationi

    • Cytoplasm UniRule annotationCurated

    GO - Cellular componenti

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi46 – 47KK → AA: Lack of activity. 3 Publications2
    Mutagenesisi46K → A: 16-fold decrease in Km for L-homoserine. 32-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi46K → L: 6-fold increase in Km for L-homoserine and in Km for succinyl-CoA. Slight increase in catalytic activity. 1 Publication1
    Mutagenesisi46K → R: Slight decrease in catalytic activity. 1 Publication1
    Mutagenesisi47K → A: 22-fold decrease in Km for L-homoserine. Almost loss of catalytic activity. 1 Publication1
    Mutagenesisi47K → L: 8-fold decrease in Km for L-homoserine and 10-fold increase in Km for succinyl-CoA. 20-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi47K → R: 14-fold decrease in Km for L-homoserine. 72-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi90C → A or S: No change in activity. 1 Publication1
    Mutagenesisi142C → A or S: Lack of activity. 2 Publications1
    Mutagenesisi157K → L: Lack of activity. 1 Publication1
    Mutagenesisi193R → A: 3-fold increase in Km for L-homoserine. 8-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi193R → K: 8-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi235H → A or N: Lack of activity. 2 Publications1
    Mutagenesisi237E → A: 32-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi237E → D: 3-fold decrease in catalytic activity. 1 Publication1
    Mutagenesisi238Y → F: 5-fold increase in Km for L-homoserine. 1 Publication1
    Mutagenesisi246E → A: 150-fold increase in Km for L-homoserine. 1 Publication1
    Mutagenesisi246E → D: 24-fold increase in Km for L-homoserine. 1 Publication1
    Mutagenesisi249R → K: 4-fold increase in Km for L-homoserine. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00001997482 – 309Homoserine O-succinyltransferaseAdd BLAST308

    Proteomic databases

    EPDiP07623.
    PaxDbiP07623.
    PRIDEiP07623.

    Expressioni

    Inductioni

    Contains two transcription starting points, P1 and P2, which are 74 bp apart. P1 is under negative control by methionine, whereas P2 is independent of the intracellular methionine concentration.1 Publication

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation1 Publication

    Protein-protein interaction databases

    BioGridi4259289. 12 interactors.
    IntActiP07623. 2 interactors.
    MINTiMINT-1343536.
    STRINGi316385.ECDH10B_4202.

    Structurei

    3D structure databases

    ProteinModelPortaliP07623.
    SMRiP07623.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the MetA family.UniRule annotationCurated

    Phylogenomic databases

    eggNOGiENOG4105CVG. Bacteria.
    COG1897. LUCA.
    HOGENOMiHOG000115049.
    InParanoidiP07623.
    KOiK00651.
    PhylomeDBiP07623.

    Family and domain databases

    CDDicd03131. GATase1_HTS. 1 hit.
    Gene3Di3.40.50.880. 1 hit.
    HAMAPiMF_00295. MetA_acyltransf. 1 hit.
    InterProiView protein in InterPro
    IPR029062. Class_I_gatase-like.
    IPR005697. Homserine_suc_trans.
    IPR033752. HTS_family.
    PANTHERiPTHR20919. PTHR20919. 1 hit.
    PTHR20919:SF1. PTHR20919:SF1. 1 hit.
    PfamiView protein in Pfam
    PF04204. HTS. 1 hit.
    PIRSFiPIRSF000450. H_ser_succinyltr. 1 hit.
    SUPFAMiSSF52317. SSF52317. 1 hit.
    TIGRFAMsiTIGR01001. metA. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P07623-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MPIRVPDELP AVNFLREENV FVMTTSRASG QEIRPLKVLI LNLMPKKIET
    60 70 80 90 100
    ENQFLRLLSN SPLQVDIQLL RIDSRESRNT PAEHLNNFYC NFEDIQDQNF
    110 120 130 140 150
    DGLIVTGAPL GLVEFNDVAY WPQIKQVLEW SKDHVTSTLF VCWAVQAALN
    160 170 180 190 200
    ILYGIPKQTR TEKLSGVYEH HILHPHALLT RGFDDSFLAP HSRYADFPAA
    210 220 230 240 250
    LIRDYTDLEI LAETEEGDAY LFASKDKRIA FVTGHPEYDA QTLAQEFFRD
    260 270 280 290 300
    VEAGLDPDVP YNYFPHNDPQ NTPRASWRSH GNLLFTNWLN YYVYQITPYD

    LRHMNPTLD
    Length:309
    Mass (Da):35,727
    Last modified:January 23, 2007 - v4
    Checksum:iA2C395A9A9CFE2C0
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti67I → V (PubMed:2654885).Curated1
    Sequence conflicti67I → V (PubMed:6094503).Curated1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X14501 Genomic DNA. Translation: CAA32654.1.
    U00006 Genomic DNA. Translation: AAC43107.1.
    U00096 Genomic DNA. Translation: AAC76983.1.
    AP009048 Genomic DNA. Translation: BAE78015.1.
    M10210 Genomic DNA. Translation: AAA24157.1.
    X12431 Genomic DNA. No translation available.
    PIRiD65208. XYECM.
    RefSeqiNP_418437.1. NC_000913.3.
    WP_001122779.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC76983; AAC76983; b4013.
    BAE78015; BAE78015; BAE78015.
    GeneIDi948513.
    KEGGiecj:JW3973.
    eco:b4013.
    PATRICifig|1411691.4.peg.2700.

    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.

    Entry informationi

    Entry nameiMETAS_ECOLI
    AccessioniPrimary (citable) accession number: P07623
    Secondary accession number(s): Q2M6U1
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
    Last sequence update: January 23, 2007
    Last modified: July 5, 2017
    This is version 146 of the entry and version 4 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. SIMILARITY comments
      Index of protein domains and families