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Protein

Inosine-5'-monophosphate dehydrogenase

Gene

guaB

Organism
Streptococcus pyogenes
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.UniRule annotation

Catalytic activityi

Inosine 5'-phosphate + NAD+ + H2O = xanthosine 5'-phosphate + NADH.UniRule annotation

Cofactori

K+UniRule annotation

Enzyme regulationi

Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.UniRule annotation

Kineticsi

  1. KM=62 µM for Inosine 5'-phosphate1 Publication
  2. KM=1180 µM for NAD+1 Publication

    pH dependencei

    Optimum pH is 7.8.1 Publication

    Pathwayi: XMP biosynthesis via de novo pathway

    This protein is involved in step 1 of the subpathway that synthesizes XMP from IMP.UniRule annotation
    Proteins known to be involved in this subpathway in this organism are:
    1. Inosine-5'-monophosphate dehydrogenase (guaB), Inosine-5'-monophosphate dehydrogenase (guaB), Inosine-5'-monophosphate dehydrogenase (guaB)
    This subpathway is part of the pathway XMP biosynthesis via de novo pathway, which is itself part of Purine metabolism.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes XMP from IMP, the pathway XMP biosynthesis via de novo pathway and in Purine metabolism.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei253NADUniRule annotation1
    Metal bindingi305Potassium; via carbonyl oxygenUniRule annotation1
    Metal bindingi307Potassium; via carbonyl oxygenUniRule annotation1
    Binding sitei308IMPUniRule annotation1 Publication1
    Active sitei310Thioimidate intermediateUniRule annotation1
    Metal bindingi310Potassium; via carbonyl oxygenUniRule annotation1
    Active sitei406Proton acceptorUniRule annotation1
    Binding sitei421IMPUniRule annotation1
    Metal bindingi475Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1
    Metal bindingi476Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1
    Metal bindingi477Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi303 – 305NADUniRule annotation3

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    GMP biosynthesis, Purine biosynthesis

    Keywords - Ligandi

    Metal-binding, NAD, Potassium

    Enzyme and pathway databases

    BRENDAi1.1.1.205. 5935.
    SABIO-RKP0C0H6.
    UniPathwayiUPA00601; UER00295.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Inosine-5'-monophosphate dehydrogenaseUniRule annotation (EC:1.1.1.205UniRule annotation)
    Short name:
    IMP dehydrogenaseUniRule annotation
    Short name:
    IMPDUniRule annotation
    Short name:
    IMPDHUniRule annotation
    Gene namesi
    Name:guaBUniRule annotation
    Synonyms:impD
    OrganismiStreptococcus pyogenes
    Taxonomic identifieri1314 [NCBI]
    Taxonomic lineageiBacteriaFirmicutesBacilliLactobacillalesStreptococcaceaeStreptococcus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi406R → A: No activity. 1 Publication1
    Mutagenesisi421E → Q: No activity. 1 Publication1
    Mutagenesisi450Y → A: No effect. 1 Publication1
    Mutagenesisi450Y → D: Reduces activity by 75%. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00000937142 – 493Inosine-5'-monophosphate dehydrogenaseAdd BLAST492

    Proteomic databases

    PaxDbiP0C0H6.
    PRIDEiP0C0H6.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation1 Publication

    Protein-protein interaction databases

    STRINGi160490.SPy_2206.

    Chemistry databases

    BindingDBiP0C0H6.

    Structurei

    Secondary structure

    1493
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi3 – 6Combined sources4
    Helixi15 – 17Combined sources3
    Beta strandi18 – 20Combined sources3
    Helixi29 – 31Combined sources3
    Beta strandi36 – 39Combined sources4
    Beta strandi42 – 50Combined sources9
    Turni54 – 56Combined sources3
    Helixi59 – 67Combined sources9
    Beta strandi71 – 74Combined sources4
    Helixi80 – 93Combined sources14
    Turni94 – 97Combined sources4
    Beta strandi98 – 100Combined sources3
    Beta strandi106 – 109Combined sources4
    Helixi110 – 119Combined sources10
    Beta strandi123 – 129Combined sources7
    Turni131 – 133Combined sources3
    Beta strandi135 – 141Combined sources7
    Helixi142 – 147Combined sources6
    Beta strandi151 – 154Combined sources4
    Turni155 – 157Combined sources3
    Helixi173 – 182Combined sources10
    Beta strandi186 – 191Combined sources6
    Beta strandi195 – 202Combined sources8
    Helixi203 – 211Combined sources9
    Beta strandi226 – 229Combined sources4
    Helixi235 – 245Combined sources11
    Beta strandi248 – 252Combined sources5
    Helixi260 – 272Combined sources13
    Beta strandi274 – 276Combined sources3
    Beta strandi278 – 283Combined sources6
    Helixi286 – 294Combined sources9
    Beta strandi298 – 302Combined sources5
    Helixi312 – 315Combined sources4
    Helixi322 – 335Combined sources14
    Beta strandi339 – 344Combined sources6
    Helixi349 – 357Combined sources9
    Beta strandi361 – 366Combined sources6
    Turni367 – 371Combined sources5
    Beta strandi372 – 374Combined sources3
    Beta strandi379 – 382Combined sources4
    Beta strandi385 – 391Combined sources7
    Helixi396 – 399Combined sources4
    Beta strandi424 – 428Combined sources5
    Helixi433 – 450Combined sources18
    Helixi456 – 462Combined sources7
    Beta strandi465 – 467Combined sources3
    Helixi470 – 476Combined sources7

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1ZFJX-ray1.90A2-492[»]
    ProteinModelPortaliP0C0H6.
    SMRiP0C0H6.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0C0H6.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini97 – 155CBS 1UniRule annotationAdd BLAST59
    Domaini159 – 219CBS 2UniRule annotationAdd BLAST61

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni343 – 345IMP binding3
    Regioni366 – 367IMP binding2
    Regioni390 – 394IMP binding5

    Sequence similaritiesi

    Belongs to the IMPDH/GMPR family.UniRule annotation
    Contains 2 CBS domains.UniRule annotation

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    eggNOGiENOG4105CP4. Bacteria.
    COG0516. LUCA.
    COG0517. LUCA.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH. 1 hit.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 2 hits.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P0C0H6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSNWDTKFLK KGYTFDDVLL IPAESHVLPN EVDLKTKLAD NLTLNIPIIT
    60 70 80 90 100
    AAMDTVTGSK MAIAIARAGG LGVIHKNMSI TEQAEEVRKV KRSENGVIID
    110 120 130 140 150
    PFFLTPEHKV SEAEELMQRY RISGVPIVET LANRKLVGII TNRDMRFISD
    160 170 180 190 200
    YNAPISEHMT SEHLVTAAVG TDLETAERIL HEHRIEKLPL VDNSGRLSGL
    210 220 230 240 250
    ITIKDIEKVI EFPHAAKDEF GRLLVAAAVG VTSDTFERAE ALFEAGADAI
    260 270 280 290 300
    VIDTAHGHSA GVLRKIAEIR AHFPNRTLIA GNIATAEGAR ALYDAGVDVV
    310 320 330 340 350
    KVGIGPGSIC TTRVVAGVGV PQVTAIYDAA AVAREYGKTI IADGGIKYSG
    360 370 380 390 400
    DIVKALAAGG NAVMLGSMFA GTDEAPGETE IYQGRKFKTY RGMGSIAAMK
    410 420 430 440 450
    KGSSDRYFQG SVNEANKLVP EGIEGRVAYK GAASDIVFQM LGGIRSGMGY
    460 470 480 490
    VGAGDIQELH ENAQFVEMSG AGLIESHPHD VQITNEAPNY SVH
    Length:493
    Mass (Da):52,807
    Last modified:January 23, 2007 - v2
    Checksum:i9C317AD598CB5740
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti419V → L no nucleotide entry (PubMed:10200156).Curated1

    Mass spectrometryi

    Molecular mass is 52328 Da from positions 2 - 493. Determined by MALDI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U26056 Genomic DNA. Translation: AAB03846.1.
    PIRiJC4372.
    RefSeqiWP_002991454.1. NZ_LVYS01000002.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U26056 Genomic DNA. Translation: AAB03846.1.
    PIRiJC4372.
    RefSeqiWP_002991454.1. NZ_LVYS01000002.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1ZFJX-ray1.90A2-492[»]
    ProteinModelPortaliP0C0H6.
    SMRiP0C0H6.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi160490.SPy_2206.

    Chemistry databases

    BindingDBiP0C0H6.

    Proteomic databases

    PaxDbiP0C0H6.
    PRIDEiP0C0H6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    eggNOGiENOG4105CP4. Bacteria.
    COG0516. LUCA.
    COG0517. LUCA.

    Enzyme and pathway databases

    UniPathwayiUPA00601; UER00295.
    BRENDAi1.1.1.205. 5935.
    SABIO-RKP0C0H6.

    Miscellaneous databases

    EvolutionaryTraceiP0C0H6.

    Family and domain databases

    CDDicd00381. IMPDH. 1 hit.
    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH. 1 hit.
    InterProiIPR013785. Aldolase_TIM.
    IPR000644. CBS_dom.
    IPR005990. IMP_DH.
    IPR015875. IMP_DH/GMP_Rdtase_CS.
    IPR001093. IMP_DH_GMPRt.
    [Graphical view]
    PANTHERiPTHR11911:SF6. PTHR11911:SF6. 2 hits.
    PfamiPF00571. CBS. 2 hits.
    PF00478. IMPDH. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000130. IMPDH. 1 hit.
    SMARTiSM00116. CBS. 2 hits.
    [Graphical view]
    TIGRFAMsiTIGR01302. IMP_dehydrog. 1 hit.
    PROSITEiPS51371. CBS. 2 hits.
    PS00487. IMP_DH_GMP_RED. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiIMDH_STRPY
    AccessioniPrimary (citable) accession number: P0C0H6
    Secondary accession number(s): P50099, P68838
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 13, 2005
    Last sequence update: January 23, 2007
    Last modified: November 2, 2016
    This is version 71 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Direct protein sequencing

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    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.