ALF_PLAFK
ID ALF_PLAFK Reviewed; 362 AA.
AC Q27744;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Fructose-bisphosphate aldolase {ECO:0000255|RuleBase:RU003994};
DE EC=4.1.2.13 {ECO:0000255|RuleBase:RU003994, ECO:0000269|PubMed:2204832, ECO:0000269|PubMed:3285469};
GN Name=FBPA {ECO:0000305}; Synonyms=p41 {ECO:0000303|PubMed:3285469};
OS Plasmodium falciparum (isolate K1 / Thailand).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5839;
RN [1] {ECO:0000312|EMBL:AAA29716.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP SUBUNIT, AND BIOTECHNOLOGY.
RC STRAIN=K1 {ECO:0000312|EMBL:AAA29716.1};
RX PubMed=3285469; DOI=10.1126/science.3285469;
RA Certa U., Ghersa P., Dobeli H., Matile H., Kocher H.P., Shrivastava I.K.,
RA Shaw A.R., Perrin L.H.;
RT "Aldolase activity of a Plasmodium falciparum protein with protective
RT properties.";
RL Science 240:1036-1038(1988).
RN [2] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, PATHWAY, SUBUNIT, INTERACTION WITH ACT2 AND HUMAN SLC4A1,
RP SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND BIOTECHNOLOGY.
RX PubMed=2204832; DOI=10.1016/0166-6851(90)90189-s;
RA Doebeli H., Trzeciak A., Gillessen D., Matile H., Srivastava I.K.,
RA Perrin L.H., Jakob P.E., Certa U.;
RT "Expression, purification, biochemical characterization and inhibition of
RT recombinant Plasmodium falciparum aldolase.";
RL Mol. Biochem. Parasitol. 41:259-268(1990).
CC -!- FUNCTION: Plays a key role in glycolysis by catalyzing the cleavage of
CC fructose 1,6-bisphosphate into dihydroxyacetone phosphate and
CC glyceraldehyde 3-phosphate (PubMed:3285469, PubMed:2204832).
CC Independently of its catalytic activity, connects the actin filaments,
CC and thus the actomyosin motor, to cell surface adhesins of the
CC thrombospondin-related anonymous protein (TRAP), the erythrocyte
CC binding ligand (EBL) and reticulocyte binding homolog (RH) protein
CC families; this interaction is probably involved in transducing the
CC motor force across the parasite surface required for sporozoite and
CC ookinete gliding motility and merozoite invasion (By similarity).
CC Stimulates actin polymerisation (By similarity).
CC {ECO:0000250|UniProtKB:Q7KQL9, ECO:0000269|PubMed:2204832,
CC ECO:0000269|PubMed:3285469}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-fructose 1,6-bisphosphate = D-glyceraldehyde 3-
CC phosphate + dihydroxyacetone phosphate; Xref=Rhea:RHEA:14729,
CC ChEBI:CHEBI:32966, ChEBI:CHEBI:57642, ChEBI:CHEBI:59776; EC=4.1.2.13;
CC Evidence={ECO:0000255|RuleBase:RU003994, ECO:0000269|PubMed:2204832,
CC ECO:0000269|PubMed:3285469};
CC -!- ACTIVITY REGULATION: The cytoplasmic tail of TRAP and probably other
CC adhesins acts as a competitive inhibitor as the binding sites of the
CC glycolytic substrate fructose 1,6-bisphosphate and TRAP partially
CC overlap (By similarity). Inhibited by suramin, an antiparasitic drug
CC used to treat Trypanosome-mediated infection (PubMed:2204832).
CC {ECO:0000250|UniProtKB:Q7KQL9, ECO:0000269|PubMed:2204832}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for fructose 1,6-bisphosphate (at pH 7.3 and with native
CC protein) {ECO:0000269|PubMed:2204832};
CC KM=25 uM for fructose 1,6-bisphosphate (at pH 7.3 and with
CC recombinant protein) {ECO:0000269|PubMed:2204832};
CC Vmax=4 umol/min/mg enzyme (with fructose 1,6-bisphosphate and at pH
CC 7.3) {ECO:0000269|PubMed:2204832};
CC Vmax=0.7 umol/min/mg enzyme (with fructose 1-phosphate and at pH 7.3)
CC {ECO:0000269|PubMed:2204832};
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 4/4.
CC {ECO:0000255|RuleBase:RU004257, ECO:0000269|PubMed:2204832,
CC ECO:0000269|PubMed:3285469}.
CC -!- SUBUNIT: Homotetramer (PubMed:3285469, PubMed:2204832). Interacts with
CC TRAP (via cytoplasmic domain); the interaction prevents substrate
CC binding and thereby inhibits aldolase activity (By similarity).
CC Interacts with MTRAP (via cytoplasmic domain); MTRAP phosphorylation
CC may increase the binding to FBPA (By similarity). Interact with RH1
CC (via cytoplasmic domain) (By similarity). Interacts with RH2b (via
CC cytoplasmic domain) (By similarity). Interacts with RH4 (via
CC cytoplasmic domain) (By similarity). Interacts with AMA1 (via
CC cytoplasmic domain); the interaction is weak, however it may be
CC increased upon AMA1 phosphorylation (By similarity). Interacts with
CC EBA140 (via cytoplasmic domain); the interaction is weak (By
CC similarity). Interacts with EBA175 (via cytoplasmic domain); the
CC interaction is weak (By similarity). Interacts with EBA181 (via
CC cytoplasmic domain); the interaction is weak (By similarity). Interacts
CC with G-actin and F-actin (By similarity). May interact with ACT2/actin
CC II; the interaction inhibits FBPA catalytic activity (PubMed:2204832).
CC Interacts with human SLC4A1/band 3 (via N-terminus); the interaction
CC inhibits FBPA catalytic activity (PubMed:2204832).
CC {ECO:0000250|UniProtKB:Q7KQL9, ECO:0000269|PubMed:2204832,
CC ECO:0000269|PubMed:3285469}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P14223}.
CC Membrane {ECO:0000250|UniProtKB:P14223}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Host cell membrane
CC {ECO:0000269|PubMed:2204832}; Peripheral membrane protein
CC {ECO:0000305}; Cytoplasmic side {ECO:0000305}.
CC -!- DEVELOPMENTAL STAGE: Expressed during parasite asexual blood stages (at
CC protein level). {ECO:0000269|PubMed:2204832}.
CC -!- BIOTECHNOLOGY: May be an effective malaria vaccine as determined by
CC epitope response in sera (PubMed:3285469). Antibodies against FBPA
CC inhibit its catalytic activity (PubMed:3285469, PubMed:2204832).
CC {ECO:0000269|PubMed:2204832, ECO:0000269|PubMed:3285469}.
CC -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC family. {ECO:0000255|RuleBase:RU003994}.
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DR EMBL; J03084; AAA29716.1; -; Genomic_DNA.
DR SMR; Q27744; -.
DR ChEMBL; CHEMBL4156; -.
DR VEuPathDB; PlasmoDB:PF3D7_1444800; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000518600; -.
DR VEuPathDB; PlasmoDB:Pf7G8_140050000; -.
DR VEuPathDB; PlasmoDB:PfCD01_140050200; -.
DR VEuPathDB; PlasmoDB:PfDd2_140049200; -.
DR VEuPathDB; PlasmoDB:PfGA01_140050300; -.
DR VEuPathDB; PlasmoDB:PfGB4_140050900; -.
DR VEuPathDB; PlasmoDB:PfGN01_140050100; -.
DR VEuPathDB; PlasmoDB:PfHB3_140050500; -.
DR VEuPathDB; PlasmoDB:PfIT_140051200; -.
DR VEuPathDB; PlasmoDB:PfKE01_140049700; -.
DR VEuPathDB; PlasmoDB:PfKH01_140050300; -.
DR VEuPathDB; PlasmoDB:PfKH02_140050500; -.
DR VEuPathDB; PlasmoDB:PfML01_140050400; -.
DR VEuPathDB; PlasmoDB:PfNF135_140048900; -.
DR VEuPathDB; PlasmoDB:PfNF166_140047700; -.
DR VEuPathDB; PlasmoDB:PfNF54_140048500; -.
DR VEuPathDB; PlasmoDB:PfSD01_140048100; -.
DR VEuPathDB; PlasmoDB:PfSN01_140052000; -.
DR VEuPathDB; PlasmoDB:PfTG01_140050100; -.
DR UniPathway; UPA00109; UER00183.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IDA:UniProtKB.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:UniProtKB.
DR GO; GO:0006096; P:glycolytic process; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR029768; Aldolase_I_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR000741; FBA_I.
DR PANTHER; PTHR11627; PTHR11627; 1.
DR Pfam; PF00274; Glycolytic; 1.
DR PROSITE; PS00158; ALDOLASE_CLASS_I; 1.
PE 1: Evidence at protein level;
KW Actin-binding; Cytoplasm; Glycolysis; Host cell membrane; Host membrane;
KW Lyase; Membrane; Schiff base.
FT CHAIN 1..362
FT /note="Fructose-bisphosphate aldolase"
FT /id="PRO_0000453627"
FT ACT_SITE 188
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT ACT_SITE 230
FT /note="Schiff-base intermediate with dihydroxyacetone-P"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT BINDING 55
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT BINDING 145
FT /ligand="beta-D-fructose 1,6-bisphosphate"
FT /ligand_id="ChEBI:CHEBI:32966"
FT /evidence="ECO:0000250|UniProtKB:P00883"
FT SITE 362
FT /note="Necessary for preference for fructose 1,6-
FT bisphosphate over fructose 1-phosphate"
FT /evidence="ECO:0000250|UniProtKB:P00883"
SQ SEQUENCE 362 AA; 39270 MW; E361038CA2998448 CRC64;
MNAPKKLPAD VAEELATTAQ KLVQAGKGIL AADESTQTIK KRFDNIKLEN TIENRASYRD
LLFGTKGLGK FISGAILFEE TLFQKNEAGV PMVNLLHNEN IIPGIKVDKG LVNIPCTDEE
KSTQGLDGLA ERCKEYYKAG ARFAKWRTVL VIDTAKGKPT DLSNHETAWG LARYASICQQ
NRLVPIVEPE ILADGPHSIE VCAVVTQKVL SCVFKALQEN GVLLEGALLK PNMVTAGYEC
TAKTTTQDVG FLTVRTLRRT VPPALPGVVF LSGGQSEEEA SVNLNSINAL GPHPWALTFS
YGRALQASVL NTWQGKKENV AKAREVLLQR AEANSLATYG KYKGGAGGEN AGASLYEKKY
VY
