FGD_MYCTU
ID FGD_MYCTU Reviewed; 336 AA.
AC P9WNE1; L0T6D5; P96253; Q7D9V4;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 46.
DE RecName: Full=F420-dependent glucose-6-phosphate dehydrogenase {ECO:0000303|PubMed:17376702};
DE Short=FGD;
DE Short=FGD1 {ECO:0000303|PubMed:17376702};
DE Short=G6PD;
DE EC=1.1.98.2 {ECO:0000269|PubMed:18434308};
GN Name=fgd1; Synonyms=fgd; OrderedLocusNames=Rv0407;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION IN THE ACTIVATION OF PA-824.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=10879539; DOI=10.1038/35016103;
RA Stover C.K., Warrener P., VanDevanter D.R., Sherman D.R., Arain T.M.,
RA Langhorne M.H., Anderson S.W., Towell J.A., Yuan Y., McMurray D.N.,
RA Kreiswirth B.N., Barry C.E., Baker W.R.;
RT "A small-molecule nitroimidazopyran drug candidate for the treatment of
RT tuberculosis.";
RL Nature 405:962-966(2000).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16387854; DOI=10.1073/pnas.0508392103;
RA Manjunatha U.H., Boshoff H., Dowd C.S., Zhang L., Albert T.J., Norton J.E.,
RA Daniels L., Dick T., Pang S.S., Barry C.E. III;
RT "Identification of a nitroimidazo-oxazine-specific protein involved in PA-
RT 824 resistance in Mycobacterium tuberculosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:431-436(2006).
RN [4]
RP SUBUNIT, AND CRYSTALLIZATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17376702; DOI=10.1016/j.pep.2007.01.014;
RA Bashiri G., Squire C.J., Baker E.N., Moreland N.J.;
RT "Expression, purification and crystallization of native and
RT selenomethionine labeled Mycobacterium tuberculosis FGD1 (Rv0407) using a
RT Mycobacterium smegmatis expression system.";
RL Protein Expr. Purif. 54:38-44(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP ROLE IN RESISTANCE TO OXIDATIVE STRESS.
RC STRAIN=ATCC 27294 / TMC 102 / H37Rv;
RX PubMed=23240649; DOI=10.1111/mmi.12127;
RA Gurumurthy M., Rao M., Mukherjee T., Rao S.P., Boshoff H.I., Dick T.,
RA Barry C.E. III, Manjunatha U.H.;
RT "A novel F(420)-dependent anti-oxidant mechanism protects Mycobacterium
RT tuberculosis against oxidative stress and bactericidal agents.";
RL Mol. Microbiol. 87:744-755(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF APOENZYME AND COMPLEX WITH
RP SUBSTRATE ANALOG AND COENZYME F420, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, REACTION MECHANISM, SUBUNIT, AND
RP ACTIVE SITE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18434308; DOI=10.1074/jbc.m801854200;
RA Bashiri G., Squire C.J., Moreland N.J., Baker E.N.;
RT "Crystal structures of F420-dependent glucose-6-phosphate dehydrogenase
RT FGD1 involved in the activation of the anti-tuberculosis drug candidate PA-
RT 824 reveal the basis of coenzyme and substrate binding.";
RL J. Biol. Chem. 283:17531-17541(2008).
CC -!- FUNCTION: Catalyzes the coenzyme F420-dependent oxidation of glucose 6-
CC phosphate to 6-phosphogluconolactone (PubMed:18434308). Appears to have
CC a role in resistance to oxidative stress, via its consumption of G6P
CC that serves as a source of reducing power to combat oxidative stress in
CC mycobacteria. More precisely, is likely involved in a F420-dependent
CC anti-oxidant mechanism that protects M.tuberculosis against oxidative
CC stress and bactericidal agents (PubMed:23240649). {ECO:0000255|HAMAP-
CC Rule:MF_02123, ECO:0000269|PubMed:18434308,
CC ECO:0000305|PubMed:23240649}.
CC -!- FUNCTION: Is essential for the bioreductive activation of the bicyclic
CC 4-nitroimidazole prodrug PA-824 (a nitroimidazo-oxazine) developed for
CC anti-tuberculosis therapy against both replicating and persistent
CC bacteria. It does not interact directly with PA-824 but, rather,
CC provides reduced F420 to the deazaflavin-dependent nitroreductase Ddn,
CC which in turn activates PA-824. {ECO:0000269|PubMed:10879539}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + H(+) + oxidized coenzyme F420-(gamma-
CC L-Glu)(n) = 6-phospho-D-glucono-1,5-lactone + reduced coenzyme F420-
CC (gamma-L-Glu)(n); Xref=Rhea:RHEA:27294, Rhea:RHEA-COMP:12939,
CC Rhea:RHEA-COMP:14378, ChEBI:CHEBI:15378, ChEBI:CHEBI:57955,
CC ChEBI:CHEBI:61548, ChEBI:CHEBI:133980, ChEBI:CHEBI:139511;
CC EC=1.1.98.2; Evidence={ECO:0000269|PubMed:18434308};
CC -!- ACTIVITY REGULATION: Inhibited by citrate.
CC {ECO:0000269|PubMed:18434308}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100 uM for glucose 6-phosphate {ECO:0000269|PubMed:18434308};
CC pH dependence:
CC Optimum pH is 6.5-7. {ECO:0000269|PubMed:18434308};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17376702,
CC ECO:0000269|PubMed:18434308}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene display a strong
CC resistance to PA-824 and CGI-17341 (a nitroimidazo-oxazole).
CC {ECO:0000269|PubMed:16387854}.
CC -!- SIMILARITY: Belongs to the F420-dependent glucose-6-phosphate
CC dehydrogenase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43138.1; -; Genomic_DNA.
DR PIR; E70628; E70628.
DR RefSeq; NP_214921.1; NC_000962.3.
DR RefSeq; WP_003898438.1; NZ_NVQJ01000002.1.
DR PDB; 3B4Y; X-ray; 1.95 A; A/B=1-336.
DR PDB; 3C8N; X-ray; 1.90 A; A/B/C/D=1-336.
DR PDBsum; 3B4Y; -.
DR PDBsum; 3C8N; -.
DR AlphaFoldDB; P9WNE1; -.
DR SMR; P9WNE1; -.
DR STRING; 83332.Rv0407; -.
DR PaxDb; P9WNE1; -.
DR DNASU; 886418; -.
DR GeneID; 886418; -.
DR KEGG; mtu:Rv0407; -.
DR TubercuList; Rv0407; -.
DR eggNOG; COG2141; Bacteria.
DR OMA; WRHKGGH; -.
DR PhylomeDB; P9WNE1; -.
DR BioCyc; MetaCyc:G185E-4532-MON; -.
DR BRENDA; 1.1.98.2; 3445.
DR Reactome; R-HSA-1222541; Cell redox homeostasis.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0070967; F:coenzyme F420 binding; IDA:MTBBASE.
DR GO; GO:0052749; F:glucose-6-phosphate dehydrogenase (coenzyme F420) activity; IEA:UniProtKB-EC.
DR GO; GO:0016614; F:oxidoreductase activity, acting on CH-OH group of donors; IDA:MTBBASE.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:UniProtKB-UniRule.
DR GO; GO:0045454; P:cell redox homeostasis; TAS:Reactome.
DR Gene3D; 3.20.20.30; -; 1.
DR HAMAP; MF_02123; F420_G6P_DH; 1.
DR InterPro; IPR019944; F420-dep_G6P_DH.
DR InterPro; IPR019945; F420_G6P_DH-rel.
DR InterPro; IPR011251; Luciferase-like_dom.
DR InterPro; IPR036661; Luciferase-like_sf.
DR Pfam; PF00296; Bac_luciferase; 1.
DR SUPFAM; SSF51679; SSF51679; 1.
DR TIGRFAMs; TIGR03554; F420_G6P_DH; 1.
DR TIGRFAMs; TIGR03557; F420_G6P_family; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carbohydrate metabolism; Oxidoreductase; Reference proteome.
FT CHAIN 1..336
FT /note="F420-dependent glucose-6-phosphate dehydrogenase"
FT /id="PRO_0000399504"
FT ACT_SITE 40
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:18434308"
FT ACT_SITE 109
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 39
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308,
FT ECO:0007744|PDB:3B4Y"
FT BINDING 76
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 107..108
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308,
FT ECO:0007744|PDB:3B4Y"
FT BINDING 112
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308,
FT ECO:0007744|PDB:3B4Y"
FT BINDING 177..178
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308,
FT ECO:0007744|PDB:3B4Y"
FT BINDING 180..181
FT /ligand="coenzyme F420-(gamma-Glu)n"
FT /ligand_id="ChEBI:CHEBI:133980"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 195
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 198
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 259
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18434308"
FT BINDING 283
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:18434308"
FT STRAND 5..10
FT /evidence="ECO:0007829|PDB:3C8N"
FT TURN 12..14
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 17..29
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 54..64
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:3C8N"
FT TURN 77..80
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 83..96
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:3C8N"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 125..142
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 179..188
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 200..205
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 207..217
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 225..235
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 239..244
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 245..253
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 256..261
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 265..273
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 277..281
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 284..289
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 290..302
FT /evidence="ECO:0007829|PDB:3C8N"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 317..327
FT /evidence="ECO:0007829|PDB:3C8N"
FT HELIX 329..333
FT /evidence="ECO:0007829|PDB:3C8N"
SQ SEQUENCE 336 AA; 36989 MW; A25059725E3A60B3 CRC64;
MAELKLGYKA SAEQFAPREL VELAVAAEAH GMDSATVSDH FQPWRHQGGH APFSLSWMTA
VGERTNRLLL GTSVLTPTFR YNPAVIAQAF ATMGCLYPNR VFLGVGTGEA LNEIATGYEG
AWPEFKERFA RLRESVGLMR QLWSGDRVDF DGDYYRLKGA SIYDVPDGGV PVYIAAGGPA
VAKYAGRAGD GFICTSGKGE ELYTEKLMPA VREGAAAADR SVDGIDKMIE IKISYDPDPE
LALNNTRFWA PLSLTAEQKH SIDDPIEMEK AADALPIEQI AKRWIVASDP DEAVEKVGQY
VTWGLNHLVF HAPGHDQRRF LELFQSDLAP RLRRLG
