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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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei253 – 2531NADUniRule annotation
    Metal bindingi305 – 3051Potassium; via carbonyl oxygenUniRule annotation
    Metal bindingi307 – 3071Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei308 – 3081IMPUniRule annotation1 Publication
    Active sitei310 – 3101Thioimidate intermediateUniRule annotation
    Metal bindingi310 – 3101Potassium; via carbonyl oxygenUniRule annotation
    Binding sitei421 – 4211IMPUniRule annotation
    Metal bindingi475 – 4751Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi476 – 4761Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation
    Metal bindingi477 – 4771Potassium; via carbonyl oxygen; shared with tetrameric partnerUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi303 – 3053NADUniRule annotation

    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)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi406 – 4061R → A: No activity. 1 Publication
    Mutagenesisi421 – 4211E → Q: No activity. 1 Publication
    Mutagenesisi450 – 4501Y → A: No effect. 1 Publication
    Mutagenesisi450 – 4501Y → D: Reduces activity by 75%. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 493492Inosine-5'-monophosphate dehydrogenasePRO_0000093714Add
    BLAST

    Proteomic databases

    PRIDEiP0C0H6.

    Interactioni

    Subunit structurei

    Homotetramer.UniRule annotation1 Publication

    Structurei

    Secondary structure

    1
    493
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 64Combined sources
    Helixi15 – 173Combined sources
    Beta strandi18 – 203Combined sources
    Helixi29 – 313Combined sources
    Beta strandi36 – 394Combined sources
    Beta strandi42 – 509Combined sources
    Turni54 – 563Combined sources
    Helixi59 – 679Combined sources
    Beta strandi71 – 744Combined sources
    Helixi80 – 9314Combined sources
    Turni94 – 974Combined sources
    Beta strandi98 – 1003Combined sources
    Beta strandi106 – 1094Combined sources
    Helixi110 – 11910Combined sources
    Beta strandi123 – 1297Combined sources
    Turni131 – 1333Combined sources
    Beta strandi135 – 1417Combined sources
    Helixi142 – 1476Combined sources
    Beta strandi151 – 1544Combined sources
    Turni155 – 1573Combined sources
    Helixi173 – 18210Combined sources
    Beta strandi186 – 1916Combined sources
    Beta strandi195 – 2028Combined sources
    Helixi203 – 2119Combined sources
    Beta strandi226 – 2294Combined sources
    Helixi235 – 24511Combined sources
    Beta strandi248 – 2525Combined sources
    Helixi260 – 27213Combined sources
    Beta strandi274 – 2763Combined sources
    Beta strandi278 – 2836Combined sources
    Helixi286 – 2949Combined sources
    Beta strandi298 – 3025Combined sources
    Helixi312 – 3154Combined sources
    Helixi322 – 33514Combined sources
    Beta strandi339 – 3446Combined sources
    Helixi349 – 3579Combined sources
    Beta strandi361 – 3666Combined sources
    Turni367 – 3715Combined sources
    Beta strandi372 – 3743Combined sources
    Beta strandi379 – 3824Combined sources
    Beta strandi385 – 3917Combined sources
    Helixi396 – 3994Combined sources
    Beta strandi424 – 4285Combined sources
    Helixi433 – 45018Combined sources
    Helixi456 – 4627Combined sources
    Beta strandi465 – 4673Combined sources
    Helixi470 – 4767Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ZFJX-ray1.90A2-492[»]
    ProteinModelPortaliP0C0H6.
    SMRiP0C0H6. Positions 2-491.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP0C0H6.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini97 – 15559CBS 1UniRule annotationAdd
    BLAST
    Domaini159 – 21961CBS 2UniRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni343 – 3453IMP binding
    Regioni366 – 3672IMP binding
    Regioni390 – 3945IMP binding

    Sequence similaritiesi

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

    Keywords - Domaini

    CBS domain, Repeat

    Phylogenomic databases

    eggNOGiCOG0517.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    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. 1 hit.
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti419 – 4191V → L no nucleotide entry (PubMed:10200156).Curated

    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_JHTQ01000034.1.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U26056 Genomic DNA. Translation: AAB03846.1.
    PIRiJC4372.
    RefSeqiWP_002991454.1. NZ_JHTQ01000034.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ZFJX-ray1.90A2-492[»]
    ProteinModelPortaliP0C0H6.
    SMRiP0C0H6. Positions 2-491.
    ModBaseiSearch...
    MobiDBiSearch...

    Chemistry

    BindingDBiP0C0H6.

    Proteomic databases

    PRIDEiP0C0H6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Phylogenomic databases

    eggNOGiCOG0517.

    Enzyme and pathway databases

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

    Miscellaneous databases

    EvolutionaryTraceiP0C0H6.

    Family and domain databases

    Gene3Di3.20.20.70. 1 hit.
    HAMAPiMF_01964. IMPDH.
    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. 1 hit.
    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...

    Publicationsi

    1. "Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase."
      Ashbaugh C.D., Wessels M.R.
      Gene 165:57-60(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Characteristics and crystal structure of bacterial inosine-5'-monophosphate dehydrogenase."
      Zhang R.G., Evans G., Rotella F.J., Westbrook E.M., Beno D., Huberman E., Joachimiak A., Collart F.R.
      Biochemistry 38:4691-4700(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-20, X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH IMP, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, SUBUNIT, MUTAGENESIS OF ARG-406; GLU-421 AND TYR-450.

    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: April 1, 2015
    This is version 62 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

    External Data

    Dasty 3

    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 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.