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Protein

Pantothenate synthetase

Gene

panC

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 condensation of pantoate with beta-alanine in an ATP-dependent reaction via a pantoyl-adenylate intermediate.1 Publication

Catalytic activityi

ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate.1 Publication

Enzyme regulationi

Pantothenate exhibits uncompetitive inhibition toward both D-pantoate and ATP, and non-competitive inhibition toward beta-alanine. AMPCPP exhibits competitive inhibition toward ATP, uncompetitive inhibition toward beta-alanine, and non-competitive inhibition toward D-pantoate. The enzyme is most active in the presence of magnesium or manganese. Other divalent cations (cobalt, nickel, zinc) are less effective.1 Publication

Kineticsi

  1. KM=130 µM for D-pantoate2 Publications
  2. KM=800 µM for beta-alanine2 Publications
  3. KM=2600 µM for ATP2 Publications
  4. KM=25.4 mM for 2-mercaptoethylamine2 Publications
  5. KM=36 mM for carbamate2 Publications
  6. KM=72 mM for 5-aminovalerate2 Publications
  7. KM=79 mM for methylamine2 Publications
  8. KM=84 mM for glycine2 Publications
  9. KM=93 mM for ethylamine2 Publications
  10. KM=103 mM for taurine2 Publications
  11. KM=108 mM for glycolate2 Publications
  12. KM=335 mM for gamma-aminobutyrate2 Publications
  13. KM=580 mM for gamma-amino-beta-hydroxybutyrate2 Publications

    Pathwayi: (R)-pantothenate biosynthesis

    This protein is involved in step 1 of the subpathway that synthesizes (R)-pantothenate from (R)-pantoate and beta-alanine.
    Proteins known to be involved in this subpathway in this organism are:
    1. Pantothenate synthetase (panC), Pantothenate synthetase (panC)
    This subpathway is part of the pathway (R)-pantothenate biosynthesis, which is itself part of Cofactor biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-pantothenate from (R)-pantoate and beta-alanine, the pathway (R)-pantothenate biosynthesis and in Cofactor biosynthesis.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei47Proton donor1
    Binding sitei72Beta-alanine1
    Binding sitei72Pantoate1
    Metal bindingi88Magnesium1
    Metal bindingi89Magnesium; via amide nitrogen1
    Metal bindingi92Magnesium1
    Binding sitei164Pantoate1
    Binding sitei187ATP; via amide nitrogen and carbonyl oxygen1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi40 – 47ATP1 Publication8
    Nucleotide bindingi158 – 161ATP1 Publication4
    Nucleotide bindingi195 – 198ATP1 Publication4

    GO - Molecular functioni

    • ATP binding Source: MTBBASE
    • cytidylate kinase activity Source: GO_Central
    • magnesium ion binding Source: MTBBASE
    • manganese ion binding Source: MTBBASE
    • pantoate-beta-alanine ligase activity Source: MTBBASE

    GO - Biological processi

    • beta-alanine metabolic process Source: MTBBASE
    • growth Source: MTBBASE
    • nucleotide phosphorylation Source: GO_Central
    • pantothenate biosynthetic process Source: MTBBASE
    • pathogenesis Source: UniProtKB-KW
    Complete GO annotation...

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Pantothenate biosynthesis, Virulence

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMTBH37RV:G185E-7881-MONOMER.
    BRENDAi6.3.2.1. 3445.
    UniPathwayiUPA00028; UER00005.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Pantothenate synthetase (EC:6.3.2.1)
    Short name:
    PS
    Alternative name(s):
    Pantoate--beta-alanine ligase
    Pantoate-activating enzyme
    Gene namesi
    Name:panC
    Ordered Locus Names:Rv3602c
    ORF Names:MTCY07H7B.20
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv3602c.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Biotechnological usei

    Subcutaneous immunization with the double panD and panC bacterial disruption mutant protects mice for over a year against subsequent virulent M.tuberculosis (strain Erdman) infections; mice show mild lung inflammation and fibrosis despite a chronic bacterila infection. This is a promising attenuated vaccine strain.1 Publication

    Disruption phenotypei

    Simultaneous disruption of panD and panC gives a mutant unable to grow in the absence of panothenate. The double mutant has a highly attenuated disease response in BALB/c and SCID mice; immunocompromised BALB/c SCID mice survive on average 36 weeks as opposed to 5 weeks for mice infected with wild-type bacteria, while immunocompetent BALB/c mice survive indefinitely. In wild-type mice bacteria grow for 3 weeks then undergo a steady decline, bacteria persist over 8 months in SCID mice (PubMed:12219086). The double mutant is sensitive to PZA but not POA in liquid culture, beta-alanine but not pantothenate antagonize the effect of PZA at pH 5.8 (PubMed:25246400).2 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi44H → A: More than 1000-fold reduction in activity and 52-fold decrease in adenylate formation. 1 Publication1
    Mutagenesisi47H → A: More than 1000-fold reduction in activity and 60-fold decrease in adenylate formation. 10-fold decrease in the affinity for ATP. 1 Publication1
    Mutagenesisi69N → A: More than 1000-fold reduction in activity and 50-fold decrease in adenylate formation. 1 Publication1
    Mutagenesisi72Q → A: More than 1000-fold reduction in activity and 45-fold decrease in adenylate formation. 1 Publication1
    Mutagenesisi77E → G: No effect. 1 Publication1
    Mutagenesisi160K → A: More than 1000-fold reduction in activity and 50-fold decrease in the affinity for ATP. 1 Publication1
    Mutagenesisi160K → C: More than 1000-fold reduction in activity and 120-fold decrease in adenylate formation. The enzymatic activity and the affinity for beta-alanine can be increased 10- and 3-fold, respectively, by alkylation of cysteine of mutant C-160. 1 Publication1
    Mutagenesisi164Q → A: 50-fold reduction in activity and slight reduction in the affinity for beta-alanine. 30- and 40-fold decrease in adenylate formation and pantothenate formation, respectively. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL6069.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemovedCombined sources1 Publication
    ChainiPRO_00001282452 – 309Pantothenate synthetaseAdd BLAST308

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylthreonineCombined sources1

    Keywords - PTMi

    Acetylation

    Proteomic databases

    PaxDbiP9WIL5.

    Interactioni

    Protein-protein interaction databases

    STRINGi83332.Rv3602c.

    Chemistry databases

    BindingDBiP9WIL5.

    Structurei

    Secondary structure

    1309
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi12 – 14Combined sources3
    Helixi17 – 29Combined sources13
    Beta strandi33 – 39Combined sources7
    Helixi45 – 55Combined sources11
    Beta strandi60 – 66Combined sources7
    Helixi70 – 72Combined sources3
    Beta strandi75 – 77Combined sources3
    Helixi78 – 81Combined sources4
    Helixi86 – 95Combined sources10
    Beta strandi100 – 102Combined sources3
    Helixi106 – 109Combined sources4
    Beta strandi116 – 119Combined sources4
    Helixi122 – 125Combined sources4
    Helixi127 – 129Combined sources3
    Helixi135 – 150Combined sources16
    Beta strandi153 – 158Combined sources6
    Helixi159 – 161Combined sources3
    Helixi162 – 174Combined sources13
    Beta strandi180 – 184Combined sources5
    Helixi199 – 201Combined sources3
    Helixi204 – 209Combined sources6
    Helixi212 – 223Combined sources12
    Helixi224 – 226Combined sources3
    Helixi228 – 240Combined sources13
    Beta strandi246 – 254Combined sources9
    Beta strandi258 – 260Combined sources3
    Beta strandi264 – 274Combined sources11
    Beta strandi277 – 286Combined sources10
    Helixi288 – 290Combined sources3
    Beta strandi294 – 296Combined sources3

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1MOPX-ray1.60A/B3-300[»]
    1N2BX-ray1.70A/B3-300[»]
    1N2EX-ray1.60A/B3-300[»]
    1N2GX-ray1.80A/B3-300[»]
    1N2HX-ray2.00A/B3-300[»]
    1N2IX-ray1.70A/B3-300[»]
    1N2JX-ray1.80A/B3-300[»]
    1N2OX-ray2.10A/B3-300[»]
    2A7XX-ray1.70A3-300[»]
    2A84X-ray1.55A3-300[»]
    2A86X-ray1.85A/B3-300[»]
    2A88X-ray1.70A3-300[»]
    3COVX-ray1.50A/B3-300[»]
    3COWX-ray1.80A/B3-300[»]
    3COYX-ray2.03A/B3-300[»]
    3COZX-ray2.00A/B3-300[»]
    3IMCX-ray1.60A/B3-300[»]
    3IMEX-ray2.39A/B3-300[»]
    3IMGX-ray1.80A/B3-300[»]
    3IOBX-ray1.80A/B3-300[»]
    3IOCX-ray2.50A/B3-300[»]
    3IODX-ray1.75A/B3-300[»]
    3IOEX-ray1.95A/B3-300[»]
    3ISJX-ray2.20A/B3-300[»]
    3IUBX-ray1.50A/B3-301[»]
    3IUEX-ray1.73A/B3-301[»]
    3IVCX-ray2.13A/B3-301[»]
    3IVGX-ray1.95A/B3-301[»]
    3IVXX-ray1.73A/B3-301[»]
    3LE8X-ray1.70A/B3-300[»]
    4DDHX-ray2.07A/B3-301[»]
    4DDKX-ray1.75A/B3-301[»]
    4DDMX-ray1.83A/B3-301[»]
    4DE5X-ray2.25A/B3-301[»]
    4EF6X-ray1.94A/B3-300[»]
    4EFKX-ray1.70A/B3-300[»]
    4FZJX-ray1.63A/B3-301[»]
    4G5FX-ray2.33A/B3-309[»]
    4G5YX-ray1.80A/B3-300[»]
    ProteinModelPortaliP9WIL5.
    SMRiP9WIL5.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the pantothenate synthetase family.Curated

    Phylogenomic databases

    eggNOGiENOG4108IAA. Bacteria.
    COG0414. LUCA.
    KOiK01918.
    OMAiNIEMQIE.
    PhylomeDBiP9WIL5.

    Family and domain databases

    CDDicd00560. PanC. 1 hit.
    Gene3Di3.40.50.620. 1 hit.
    HAMAPiMF_00158. PanC. 1 hit.
    InterProiIPR003721. Pantoate_ligase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PfamiPF02569. Pantoate_ligase. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00018. panC. 1 hit.

    Sequencei

    Sequence statusi: Complete.

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

    P9WIL5-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTIPAFHPGE LNVYSAPGDV ADVSRALRLT GRRVMLVPTM GALHEGHLAL
    60 70 80 90 100
    VRAAKRVPGS VVVVSIFVNP MQFGAGEDLD AYPRTPDDDL AQLRAEGVEI
    110 120 130 140 150
    AFTPTTAAMY PDGLRTTVQP GPLAAELEGG PRPTHFAGVL TVVLKLLQIV
    160 170 180 190 200
    RPDRVFFGEK DYQQLVLIRQ LVADFNLDVA VVGVPTVREA DGLAMSSRNR
    210 220 230 240 250
    YLDPAQRAAA VALSAALTAA AHAATAGAQA ALDAARAVLD AAPGVAVDYL
    260 270 280 290 300
    ELRDIGLGPM PLNGSGRLLV AARLGTTRLL DNIAIEIGTF AGTDRPDGYR

    AILESHWRN
    Length:309
    Mass (Da):32,678
    Last modified:April 16, 2014 - v1
    Checksum:iEB51DBE3485F970A
    GO

    Mass spectrometryi

    Molecular mass is 32545 Da from positions 2 - 309. Determined by ESI. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46425.1.
    PIRiC70955.
    RefSeqiNP_218119.1. NC_000962.3.
    WP_003419526.1. NZ_KK339374.1.

    Genome annotation databases

    EnsemblBacteriaiCCP46425; CCP46425; Rv3602c.
    GeneIDi885459.
    KEGGimtu:Rv3602c.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP46425.1.
    PIRiC70955.
    RefSeqiNP_218119.1. NC_000962.3.
    WP_003419526.1. NZ_KK339374.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1MOPX-ray1.60A/B3-300[»]
    1N2BX-ray1.70A/B3-300[»]
    1N2EX-ray1.60A/B3-300[»]
    1N2GX-ray1.80A/B3-300[»]
    1N2HX-ray2.00A/B3-300[»]
    1N2IX-ray1.70A/B3-300[»]
    1N2JX-ray1.80A/B3-300[»]
    1N2OX-ray2.10A/B3-300[»]
    2A7XX-ray1.70A3-300[»]
    2A84X-ray1.55A3-300[»]
    2A86X-ray1.85A/B3-300[»]
    2A88X-ray1.70A3-300[»]
    3COVX-ray1.50A/B3-300[»]
    3COWX-ray1.80A/B3-300[»]
    3COYX-ray2.03A/B3-300[»]
    3COZX-ray2.00A/B3-300[»]
    3IMCX-ray1.60A/B3-300[»]
    3IMEX-ray2.39A/B3-300[»]
    3IMGX-ray1.80A/B3-300[»]
    3IOBX-ray1.80A/B3-300[»]
    3IOCX-ray2.50A/B3-300[»]
    3IODX-ray1.75A/B3-300[»]
    3IOEX-ray1.95A/B3-300[»]
    3ISJX-ray2.20A/B3-300[»]
    3IUBX-ray1.50A/B3-301[»]
    3IUEX-ray1.73A/B3-301[»]
    3IVCX-ray2.13A/B3-301[»]
    3IVGX-ray1.95A/B3-301[»]
    3IVXX-ray1.73A/B3-301[»]
    3LE8X-ray1.70A/B3-300[»]
    4DDHX-ray2.07A/B3-301[»]
    4DDKX-ray1.75A/B3-301[»]
    4DDMX-ray1.83A/B3-301[»]
    4DE5X-ray2.25A/B3-301[»]
    4EF6X-ray1.94A/B3-300[»]
    4EFKX-ray1.70A/B3-300[»]
    4FZJX-ray1.63A/B3-301[»]
    4G5FX-ray2.33A/B3-309[»]
    4G5YX-ray1.80A/B3-300[»]
    ProteinModelPortaliP9WIL5.
    SMRiP9WIL5.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv3602c.

    Chemistry databases

    BindingDBiP9WIL5.
    ChEMBLiCHEMBL6069.

    Proteomic databases

    PaxDbiP9WIL5.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP46425; CCP46425; Rv3602c.
    GeneIDi885459.
    KEGGimtu:Rv3602c.

    Organism-specific databases

    TubercuListiRv3602c.

    Phylogenomic databases

    eggNOGiENOG4108IAA. Bacteria.
    COG0414. LUCA.
    KOiK01918.
    OMAiNIEMQIE.
    PhylomeDBiP9WIL5.

    Enzyme and pathway databases

    UniPathwayiUPA00028; UER00005.
    BioCyciMTBH37RV:G185E-7881-MONOMER.
    BRENDAi6.3.2.1. 3445.

    Family and domain databases

    CDDicd00560. PanC. 1 hit.
    Gene3Di3.40.50.620. 1 hit.
    HAMAPiMF_00158. PanC. 1 hit.
    InterProiIPR003721. Pantoate_ligase.
    IPR014729. Rossmann-like_a/b/a_fold.
    [Graphical view]
    PfamiPF02569. Pantoate_ligase. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00018. panC. 1 hit.
    ProtoNetiSearch...

    Entry informationi

    Entry nameiPANC_MYCTU
    AccessioniPrimary (citable) accession number: P9WIL5
    Secondary accession number(s): L0TG74, O06280, P0A5R0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: November 30, 2016
    This is version 24 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Miscellaneous

    The reaction proceeds by a bi uni uni bi ping pong mechanism.
    Was identified as a high-confidence drug target.

    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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.