GLUPH_PLAF7
ID GLUPH_PLAF7 Reviewed; 910 AA.
AC Q8IKU0; A0A144A6N0;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Bifunctional glucose-6-phosphate 1-dehydrogenase/6-phosphogluconolactonase {ECO:0000303|PubMed:21443518};
DE Short=PfGluPho {ECO:0000303|PubMed:21443518};
DE Includes:
DE RecName: Full=6-phosphogluconolactonase {ECO:0000303|PubMed:21443518};
DE Short=6PGL {ECO:0000303|PubMed:21443518};
DE EC=3.1.1.31 {ECO:0000269|PubMed:21443518};
DE Includes:
DE RecName: Full=Glucose-6-phosphate 1-dehydrogenase {ECO:0000303|PubMed:21443518};
DE Short=G6PD {ECO:0000303|PubMed:21443518};
DE EC=1.1.1.49 {ECO:0000269|PubMed:21443518};
GN Name=GluPho {ECO:0000305}; ORFNames=PF14_0511, PF3D7_1453800;
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7;
RX PubMed=12368864; DOI=10.1038/nature01097;
RA Gardner M.J., Hall N., Fung E., White O., Berriman M., Hyman R.W.,
RA Carlton J.M., Pain A., Nelson K.E., Bowman S., Paulsen I.T., James K.D.,
RA Eisen J.A., Rutherford K.M., Salzberg S.L., Craig A., Kyes S., Chan M.-S.,
RA Nene V., Shallom S.J., Suh B., Peterson J., Angiuoli S., Pertea M.,
RA Allen J., Selengut J., Haft D., Mather M.W., Vaidya A.B., Martin D.M.A.,
RA Fairlamb A.H., Fraunholz M.J., Roos D.S., Ralph S.A., McFadden G.I.,
RA Cummings L.M., Subramanian G.M., Mungall C., Venter J.C., Carucci D.J.,
RA Hoffman S.L., Newbold C., Davis R.W., Fraser C.M., Barrell B.G.;
RT "Genome sequence of the human malaria parasite Plasmodium falciparum.";
RL Nature 419:498-511(2002).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RC STRAIN=3D7 {ECO:0000269|PubMed:21443518};
RX PubMed=21443518; DOI=10.1042/bj20110170;
RA Jortzik E., Mailu B.M., Preuss J., Fischer M., Bode L., Rahlfs S.,
RA Becker K.;
RT "Glucose-6-phosphate dehydrogenase-6-phosphogluconolactonase: a unique
RT bifunctional enzyme from Plasmodium falciparum.";
RL Biochem. J. 436:641-650(2011).
CC -!- FUNCTION: Bifunctional enzyme which catalyzes the first two steps of
CC the oxidative pentose-phosphate pathway, which represents a route for
CC the dissimilation of carbohydrates besides glycolysis. The main
CC function of this enzyme is to provide reducing power (NADPH) and
CC pentose phosphates for fatty acid and nucleic acid synthesis.
CC {ECO:0000269|PubMed:21443518}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=6-phospho-D-glucono-1,5-lactone + H2O = 6-phospho-D-gluconate
CC + H(+); Xref=Rhea:RHEA:12556, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57955, ChEBI:CHEBI:58759; EC=3.1.1.31;
CC Evidence={ECO:0000269|PubMed:21443518};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-glucose 6-phosphate + NADP(+) = 6-phospho-D-glucono-1,5-
CC lactone + H(+) + NADPH; Xref=Rhea:RHEA:15841, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:57955, ChEBI:CHEBI:58349,
CC ChEBI:CHEBI:61548; EC=1.1.1.49;
CC Evidence={ECO:0000269|PubMed:21443518};
CC -!- ACTIVITY REGULATION: G6PD activity is inhibited by glucosamine-6-
CC phosphate, NADPH, and 4-(4-bromophenyl)-7-(3,4-dimethoxyphenyl)-
CC 4,6,7,8-tetrahydroquinoline-2,5(1 H,3H)-dione. G6PD and 6PGL activities
CC can be reversibly inhibited by S-glutathionylation (in vitro).
CC {ECO:0000269|PubMed:21443518}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=19.2 uM for glucose-6-phosphate (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:21443518};
CC KM=6.5 uM for NADP(+) (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:21443518};
CC KM=172 uM for 6-phosphoglucono-gamma-lactone (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:21443518};
CC Vmax=5.2 umol/min/mg enzyme towards glucose-6-phosphate (at 25
CC degrees Celsius) {ECO:0000269|PubMed:21443518};
CC Vmax=4.6 umol/min/mg enzyme towards NADP(+) (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:21443518};
CC Vmax=46.6 umol/min/mg enzyme with 6-phosphoglucono-gamma-lactone as
CC substrate (at 25 degrees Celsius) {ECO:0000269|PubMed:21443518};
CC pH dependence:
CC Optimum pH is 8.0 for G6PD activity. {ECO:0000269|PubMed:21443518};
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC 1/3. {ECO:0000269|PubMed:21443518}.
CC -!- PATHWAY: Carbohydrate degradation; pentose phosphate pathway; D-
CC ribulose 5-phosphate from D-glucose 6-phosphate (oxidative stage): step
CC 2/3. {ECO:0000269|PubMed:21443518}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:21443518}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the
CC glucosamine/galactosamine-6-phosphate isomerase family. 6-
CC phosphogluconolactonase subfamily. {ECO:0000255}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the glucose-6-
CC phosphate dehydrogenase family. {ECO:0000255}.
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DR EMBL; LN999946; CZU00233.1; -; Genomic_DNA.
DR PIR; S40259; S40259.
DR PIR; S47533; S47533.
DR RefSeq; XP_001348685.1; XM_001348649.2.
DR AlphaFoldDB; Q8IKU0; -.
DR SMR; Q8IKU0; -.
DR STRING; 5833.PF14_0511; -.
DR BindingDB; Q8IKU0; -.
DR ChEMBL; CHEMBL4295620; -.
DR PRIDE; Q8IKU0; -.
DR EnsemblProtists; CZU00233; CZU00233; PF3D7_1453800.
DR GeneID; 812093; -.
DR KEGG; pfa:PF3D7_1453800; -.
DR VEuPathDB; PlasmoDB:PF3D7_1453800; -.
DR HOGENOM; CLU_013524_3_0_1; -.
DR InParanoid; Q8IKU0; -.
DR OMA; MYNNEFV; -.
DR PhylomeDB; Q8IKU0; -.
DR BRENDA; 1.1.1.49; 4889.
DR BRENDA; 3.1.1.31; 4889.
DR Reactome; R-PFA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-PFA-71336; Pentose phosphate pathway.
DR UniPathway; UPA00115; UER00408.
DR UniPathway; UPA00115; UER00409.
DR Proteomes; UP000001450; Chromosome 14.
DR GO; GO:0017057; F:6-phosphogluconolactonase activity; ISS:GeneDB.
DR GO; GO:0004345; F:glucose-6-phosphate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0050661; F:NADP binding; IEA:InterPro.
DR GO; GO:0051156; P:glucose 6-phosphate metabolic process; TAS:GeneDB.
DR GO; GO:0006006; P:glucose metabolic process; IBA:GO_Central.
DR GO; GO:0006098; P:pentose-phosphate shunt; TAS:GeneDB.
DR GO; GO:0009051; P:pentose-phosphate shunt, oxidative branch; IBA:GO_Central.
DR HAMAP; MF_00966; G6PD; 1.
DR InterPro; IPR001282; G6P_DH.
DR InterPro; IPR022675; G6P_DH_C.
DR InterPro; IPR022674; G6P_DH_NAD-bd.
DR InterPro; IPR006148; Glc/Gal-6P_isomerase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR037171; NagB/RpiA_transferase-like.
DR PANTHER; PTHR23429; PTHR23429; 1.
DR Pfam; PF02781; G6PD_C; 1.
DR Pfam; PF00479; G6PD_N; 2.
DR Pfam; PF01182; Glucosamine_iso; 1.
DR PRINTS; PR00079; G6PDHDRGNASE.
DR SUPFAM; SSF100950; SSF100950; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
PE 1: Evidence at protein level;
KW Carbohydrate metabolism; Glucose metabolism; Glutathionylation; Hydrolase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Reference proteome.
FT CHAIN 1..910
FT /note="Bifunctional glucose-6-phosphate 1-dehydrogenase/6-
FT phosphogluconolactonase"
FT /id="PRO_0000424558"
FT REGION 1..170
FT /note="6-phosphogluconolactonase"
FT /evidence="ECO:0000255"
FT REGION 171..276
FT /note="Linker"
FT /evidence="ECO:0000255"
FT REGION 277..910
FT /note="Glucose-6-phosphate 1-dehydrogenase"
FT /evidence="ECO:0000255"
FT REGION 689..711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 640
FT /note="Proton acceptor; for G6PD activity"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 345..352
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 379
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 548
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 548
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 578..582
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 616
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 635
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 745
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
FT BINDING 779
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P11413"
SQ SEQUENCE 910 AA; 106987 MW; 00BF883431E018A4 CRC64;
MDYENFVKSA EEINNLHNVN YLETKDLNDF NWKAAYYICK EIYDKQQINK DGYVVIGLSG
GRTPIDVYKN MCLIKDIKID KSKLIFFIID ERYKSDDHKF SNYNNIKFLF HNLNINEKEQ
LYKPDTTKSI VDCILDYNDK IKIMIEKYKK VDIAILGMGS DFHIASLFPN IFYNIYMNNY
QNNYIYNEKT LDFINNDQDN DNLKYLKEYV YFTTTNQFDV RKRITVSLNL LANASSKIFL
LNSKDKLDLW KNMLIKSYIE VNYNLYPATY LIDTSCTNEN VNINNNNNNN NKNKNNYCYS
NTTVISCGYE NYTKSIEEIY DSKYALSLYS NSLNKEELLT IIIFGCSGDL AKKKIYPALF
KLFCNNSLPK DLLIIGFART VQDFDTFFDK IVIYLKRCLL CYEDWSISKK KDLLNGFKNR
CRYFVGNYSS SESFENFNKY LTTIEEEEAK KKYYATCYKM NGSDYNISNN VAEDNISIDD
ENKTNEYFQM CTPKNCPDNV FSSNYNFPYV INRMLYLALP PHIFVSTLKN YKKNCLNSKG
TDKILLEKPF GNDLDSFKML SKQILENFNE QQIYRIDHYL GKDMVSGLLK LKFTNTFLLS
LMNRHFIKCI KITLKETKGV YGRGQYFDPY GIIRDVMQNH MLQLLTLITM EDPIDLNDES
VKNEKIKILK SIPSIKLEDT IIGQYEKAEN FKEDENNDDE SKKNHSYHDD PHIDKNSITP
TFCTCILYIN SINWYGVPII FKSGKGLNKD ICEIRIQFHN IMGSSDENMN NNEFVIILQP
VEAIYLKMMI KKTGCEEMEE VQLNLTVNEK NKKINVPEAY ETLLLECFKG HKKKFISDEE
LYESWRIFTP LLKELQEKQV KPLKYSFGSS GPKEVFGLVK KYYNYGKNYT HRPEFVRKSS
FYEDDLLDIN
