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Protein

F420-dependent glucose-6-phosphate dehydrogenase

Gene

fgd1

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 coenzyme F420-dependent oxidation of glucose 6-phosphate to 6-phosphogluconolactone (PubMed:18434308). Appears to have a role in resistance to oxidative stress, via its consumption of G6P that serves as a source of reducing power to combat oxidative stress in mycobacteria. More precisely, is likely involved in a F420-dependent anti-oxidant mechanism that protects M.tuberculosis against oxidative stress and bactericidal agents (PubMed:23240649).UniRule annotation1 Publication1 Publication
Is essential for the bioreductive activation of the bicyclic 4-nitroimidazole prodrug PA-824 (a nitroimidazo-oxazine) developed for anti-tuberculosis therapy against both replicating and persistent bacteria. It does not interact directly with PA-824 but, rather, provides reduced F420 to the deazaflavin-dependent nitroreductase Ddn, which in turn activates PA-824.1 Publication

Catalytic activityi

D-glucose 6-phosphate + oxidized coenzyme F420 = D-glucono-1,5-lactone 6-phosphate + reduced coenzyme F420.1 Publication

Enzyme regulationi

Inhibited by citrate.1 Publication

Kineticsi

  1. KM=100 µM for glucose 6-phosphate1 Publication

    pH dependencei

    Optimum pH is 6.5-7.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei39 – 391F420Combined sources1 Publication
    Active sitei40 – 401Proton donor1 Publication
    Binding sitei76 – 761F4201 Publication
    Active sitei109 – 1091Proton acceptor1 Publication
    Binding sitei112 – 1121F420Combined sources1 Publication
    Binding sitei195 – 1951Substrate1 Publication
    Binding sitei198 – 1981Substrate1 Publication
    Binding sitei259 – 2591Substrate1 Publication
    Binding sitei283 – 2831Substrate1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Carbohydrate metabolism

    Enzyme and pathway databases

    ReactomeiR-HSA-1222541. Cell redox homeostasis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    F420-dependent glucose-6-phosphate dehydrogenase1 Publication (EC:1.1.98.21 Publication)
    Short name:
    FGD
    Short name:
    FGD11 Publication
    Short name:
    G6PD
    Gene namesi
    Name:fgd1
    Synonyms:fgd
    Ordered Locus Names:Rv0407
    OrganismiMycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
    Taxonomic identifieri83332 [NCBI]
    Taxonomic lineageiBacteriaActinobacteriaCorynebacterialesMycobacteriaceaeMycobacteriumMycobacterium tuberculosis complex
    Proteomesi
    • UP000001584 Componenti: Chromosome

    Organism-specific databases

    TubercuListiRv0407.

    Subcellular locationi

    GO - Cellular componenti

    • cell wall Source: MTBBASE
    • cytosol Source: Reactome
    • plasma membrane Source: MTBBASE
    Complete GO annotation...

    Pathology & Biotechi

    Disruption phenotypei

    Cells lacking this gene display a strong resistance to PA-824 and CGI-17341 (a nitroimidazo-oxazole).1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 336336F420-dependent glucose-6-phosphate dehydrogenasePRO_0000399504Add
    BLAST

    Proteomic databases

    PaxDbiP9WNE1.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Protein-protein interaction databases

    STRINGi83332.Rv0407.

    Structurei

    Secondary structure

    1
    336
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi5 – 106Combined sources
    Turni12 – 143Combined sources
    Helixi17 – 2913Combined sources
    Beta strandi33 – 375Combined sources
    Helixi54 – 6411Combined sources
    Beta strandi69 – 735Combined sources
    Turni77 – 804Combined sources
    Helixi83 – 9614Combined sources
    Beta strandi101 – 1055Combined sources
    Helixi110 – 1134Combined sources
    Turni114 – 1174Combined sources
    Helixi125 – 14218Combined sources
    Beta strandi148 – 1514Combined sources
    Beta strandi156 – 1605Combined sources
    Beta strandi172 – 1754Combined sources
    Helixi179 – 18810Combined sources
    Beta strandi190 – 1956Combined sources
    Helixi200 – 2056Combined sources
    Helixi207 – 21711Combined sources
    Helixi222 – 2243Combined sources
    Beta strandi225 – 23511Combined sources
    Helixi239 – 2446Combined sources
    Helixi245 – 2539Combined sources
    Helixi256 – 2616Combined sources
    Helixi265 – 2739Combined sources
    Helixi277 – 2815Combined sources
    Beta strandi284 – 2896Combined sources
    Helixi290 – 30213Combined sources
    Beta strandi307 – 3115Combined sources
    Helixi317 – 32711Combined sources
    Helixi329 – 3335Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3B4YX-ray1.95A/B1-336[»]
    3C8NX-ray1.90A/B/C/D1-336[»]
    ProteinModelPortaliP9WNE1.
    SMRiP9WNE1. Positions 3-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni107 – 1082F420 bindingCombined sources1 Publication
    Regioni177 – 1782F420 bindingCombined sources1 Publication
    Regioni180 – 1812F420 binding1 Publication

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG41079Y2. Bacteria.
    COG2141. LUCA.
    KOiK15510.
    OMAiGKGMDLY.
    PhylomeDBiP9WNE1.

    Family and domain databases

    Gene3Di3.20.20.30. 1 hit.
    HAMAPiMF_02123. F420_G6P_DH.
    InterProiIPR019944. F420-dep_G6P_DH.
    IPR019945. F420_G6P_DH-rel.
    IPR011251. Luciferase-like_dom.
    [Graphical view]
    PfamiPF00296. Bac_luciferase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51679. SSF51679. 1 hit.
    TIGRFAMsiTIGR03554. F420_G6P_DH. 1 hit.
    TIGR03557. F420_G6P_family. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P9WNE1-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MAELKLGYKA SAEQFAPREL VELAVAAEAH GMDSATVSDH FQPWRHQGGH
    60 70 80 90 100
    APFSLSWMTA VGERTNRLLL GTSVLTPTFR YNPAVIAQAF ATMGCLYPNR
    110 120 130 140 150
    VFLGVGTGEA LNEIATGYEG AWPEFKERFA RLRESVGLMR QLWSGDRVDF
    160 170 180 190 200
    DGDYYRLKGA SIYDVPDGGV PVYIAAGGPA VAKYAGRAGD GFICTSGKGE
    210 220 230 240 250
    ELYTEKLMPA VREGAAAADR SVDGIDKMIE IKISYDPDPE LALNNTRFWA
    260 270 280 290 300
    PLSLTAEQKH SIDDPIEMEK AADALPIEQI AKRWIVASDP DEAVEKVGQY
    310 320 330
    VTWGLNHLVF HAPGHDQRRF LELFQSDLAP RLRRLG
    Length:336
    Mass (Da):36,989
    Last modified:April 16, 2014 - v1
    Checksum:iA25059725E3A60B3
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP43138.1.
    PIRiE70628.
    RefSeqiNP_214921.1. NC_000962.3.
    WP_003898438.1. NZ_KK339370.1.

    Genome annotation databases

    EnsemblBacteriaiCCP43138; CCP43138; Rv0407.
    GeneIDi886418.
    KEGGimtu:Rv0407.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AL123456 Genomic DNA. Translation: CCP43138.1.
    PIRiE70628.
    RefSeqiNP_214921.1. NC_000962.3.
    WP_003898438.1. NZ_KK339370.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3B4YX-ray1.95A/B1-336[»]
    3C8NX-ray1.90A/B/C/D1-336[»]
    ProteinModelPortaliP9WNE1.
    SMRiP9WNE1. Positions 3-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi83332.Rv0407.

    Proteomic databases

    PaxDbiP9WNE1.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiCCP43138; CCP43138; Rv0407.
    GeneIDi886418.
    KEGGimtu:Rv0407.

    Organism-specific databases

    TubercuListiRv0407.

    Phylogenomic databases

    eggNOGiENOG41079Y2. Bacteria.
    COG2141. LUCA.
    KOiK15510.
    OMAiGKGMDLY.
    PhylomeDBiP9WNE1.

    Enzyme and pathway databases

    ReactomeiR-HSA-1222541. Cell redox homeostasis.

    Family and domain databases

    Gene3Di3.20.20.30. 1 hit.
    HAMAPiMF_02123. F420_G6P_DH.
    InterProiIPR019944. F420-dep_G6P_DH.
    IPR019945. F420_G6P_DH-rel.
    IPR011251. Luciferase-like_dom.
    [Graphical view]
    PfamiPF00296. Bac_luciferase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51679. SSF51679. 1 hit.
    TIGRFAMsiTIGR03554. F420_G6P_DH. 1 hit.
    TIGR03557. F420_G6P_family. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: ATCC 25618 / H37Rv.
    2. Cited for: FUNCTION IN THE ACTIVATION OF PA-824.
      Strain: ATCC 27294 / TMC 102 / H37Rv.
    3. "Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in Mycobacterium tuberculosis."
      Manjunatha U.H., Boshoff H., Dowd C.S., Zhang L., Albert T.J., Norton J.E., Daniels L., Dick T., Pang S.S., Barry C.E. III
      Proc. Natl. Acad. Sci. U.S.A. 103:431-436(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE.
    4. "Expression, purification and crystallization of native and selenomethionine labeled Mycobacterium tuberculosis FGD1 (Rv0407) using a Mycobacterium smegmatis expression system."
      Bashiri G., Squire C.J., Baker E.N., Moreland N.J.
      Protein Expr. Purif. 54:38-44(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBUNIT, CRYSTALLIZATION.
      Strain: ATCC 25618 / H37Rv.
    5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Strain: ATCC 25618 / H37Rv.
    6. "A novel F(420)-dependent anti-oxidant mechanism protects Mycobacterium tuberculosis against oxidative stress and bactericidal agents."
      Gurumurthy M., Rao M., Mukherjee T., Rao S.P., Boshoff H.I., Dick T., Barry C.E. III, Manjunatha U.H.
      Mol. Microbiol. 87:744-755(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN RESISTANCE TO OXIDATIVE STRESS.
      Strain: ATCC 27294 / TMC 102 / H37Rv.
    7. "Crystal structures of F420-dependent glucose-6-phosphate dehydrogenase FGD1 involved in the activation of the anti-tuberculosis drug candidate PA-824 reveal the basis of coenzyme and substrate binding."
      Bashiri G., Squire C.J., Moreland N.J., Baker E.N.
      J. Biol. Chem. 283:17531-17541(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOENZYME AND COMPLEX WITH SUBSTRATE ANALOG AND COENZYME F420, FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, REACTION MECHANISM, SUBUNIT, ACTIVE SITE.
      Strain: ATCC 25618 / H37Rv.

    Entry informationi

    Entry nameiFGD_MYCTU
    AccessioniPrimary (citable) accession number: P9WNE1
    Secondary accession number(s): L0T6D5, P96253, Q7D9V4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 16, 2014
    Last sequence update: April 16, 2014
    Last modified: December 9, 2015
    This is version 18 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, 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. 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.