ISPH_PLAF7
ID ISPH_PLAF7 Reviewed; 535 AA.
AC Q8I295; Q9BJX6;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=4-hydroxy-3-methylbut-2-enyl diphosphate reductase, apicoplast {ECO:0000303|PubMed:16289098};
DE Short=HMBPP reductase {ECO:0000303|PubMed:16289098};
DE EC=1.17.7.4 {ECO:0000269|PubMed:16289098};
DE Flags: Precursor;
GN Name=LytB {ECO:0000303|PubMed:16289098};
GN Synonyms=IspH {ECO:0000303|PubMed:16289098};
GN ORFNames=PF3D7_0104400 {ECO:0000312|EMBL:CAD49005.1};
OS Plasmodium falciparum (isolate 3D7).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=36329 {ECO:0000312|Proteomes:UP000001450};
RN [1] {ECO:0000312|EMBL:AAK12102.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=11274098; DOI=10.1128/jb.183.8.2411-2416.2001;
RA Altincicek B., Kollas A.-K., Sanderbrand S., Wiesner J., Hintz M., Beck E.,
RA Jomaa H.;
RT "GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of
RT isoprenoid biosynthesis in Escherichia coli.";
RL J. Bacteriol. 183:2411-2416(2001).
RN [2] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
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 [3] {ECO:0000312|Proteomes:UP000001450}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=3D7 {ECO:0000312|Proteomes:UP000001450};
RX PubMed=12368867; DOI=10.1038/nature01095;
RA Hall N., Pain A., Berriman M., Churcher C.M., Harris B., Harris D.,
RA Mungall K.L., Bowman S., Atkin R., Baker S., Barron A., Brooks K.,
RA Buckee C.O., Burrows C., Cherevach I., Chillingworth C., Chillingworth T.,
RA Christodoulou Z., Clark L., Clark R., Corton C., Cronin A., Davies R.M.,
RA Davis P., Dear P., Dearden F., Doggett J., Feltwell T., Goble A.,
RA Goodhead I., Gwilliam R., Hamlin N., Hance Z., Harper D., Hauser H.,
RA Hornsby T., Holroyd S., Horrocks P., Humphray S., Jagels K., James K.D.,
RA Johnson D., Kerhornou A., Knights A., Konfortov B., Kyes S., Larke N.,
RA Lawson D., Lennard N., Line A., Maddison M., Mclean J., Mooney P.,
RA Moule S., Murphy L., Oliver K., Ormond D., Price C., Quail M.A.,
RA Rabbinowitsch E., Rajandream M.A., Rutter S., Rutherford K.M., Sanders M.,
RA Simmonds M., Seeger K., Sharp S., Smith R., Squares R., Squares S.,
RA Stevens K., Taylor K., Tivey A., Unwin L., Whitehead S., Woodward J.R.,
RA Sulston J.E., Craig A., Newbold C., Barrell B.G.;
RT "Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.";
RL Nature 419:527-531(2002).
RN [4] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP INTERACTION WITH FD.
RX PubMed=16289098; DOI=10.1016/j.febslet.2005.10.037;
RA Roehrich R.C., Englert N., Troschke K., Reichenberg A., Hintz M.,
RA Seeber F., Balconi E., Aliverti A., Zanetti G., Koehler U., Pfeiffer M.,
RA Beck E., Jomaa H., Wiesner J.;
RT "Reconstitution of an apicoplast-localised electron transfer pathway
RT involved in the isoprenoid biosynthesis of Plasmodium falciparum.";
RL FEBS Lett. 579:6433-6438(2005).
RN [5] {ECO:0007744|PDB:4N7B}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP (3FE-4S).
RX PubMed=24188825; DOI=10.1016/j.febslet.2013.10.029;
RA Rekittke I., Olkhova E., Wiesner J., Demmer U., Warkentin E., Jomaa H.,
RA Ermler U.;
RT "Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase
RT from Plasmodium falciparum.";
RL FEBS Lett. 587:3968-3972(2013).
CC -!- FUNCTION: Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl
CC 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP)
CC and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the
CC DOXP/MEP pathway for isoprenoid precursor biosynthesis.
CC {ECO:0000269|PubMed:16289098}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + H2O + 2 oxidized [2Fe-2S]-
CC [ferredoxin] = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H(+)
CC + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:24825, Rhea:RHEA-
CC COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:57623, ChEBI:CHEBI:128753; EC=1.17.7.4;
CC Evidence={ECO:0000269|PubMed:16289098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + isopentenyl diphosphate + 2 oxidized [2Fe-2S]-
CC [ferredoxin] = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H(+)
CC + 2 reduced [2Fe-2S]-[ferredoxin]; Xref=Rhea:RHEA:24488, Rhea:RHEA-
CC COMP:10000, Rhea:RHEA-COMP:10001, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738,
CC ChEBI:CHEBI:128753, ChEBI:CHEBI:128769; EC=1.17.7.4;
CC Evidence={ECO:0000269|PubMed:16289098};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:24188825};
CC Note=Was shown to bind 1 [3Fe-4S] cluster (PubMed:24188825). However,
CC it initially contains a [4Fe-4S] cluster which easily degrades into a
CC [3Fe-4S] form in the presence of oxygen (Probable).
CC {ECO:0000269|PubMed:24188825, ECO:0000305|PubMed:24188825};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=39 uM for (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate (HMBPP)
CC (with methyl viologen as electron donor and at 30 degrees Celsius)
CC {ECO:0000269|PubMed:16289098};
CC Vmax=2.1 umol/min/mg enzyme for (2E)-4-hydroxy-3-methylbut-2-enyl
CC diphosphate (HMBPP) (with methyl viologen as electron donor and at 30
CC degrees Celsius) {ECO:0000269|PubMed:16289098};
CC Note=kcat is 1.3 sec(-1) for (2E)-4-hydroxy-3-methylbut-2-enyl
CC diphosphate (HMBPP) (with methyl viologen as electron donor and at 30
CC degrees Celsius). {ECO:0000269|PubMed:16289098};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius.
CC {ECO:0000269|PubMed:16289098};
CC -!- PATHWAY: Isoprenoid biosynthesis; dimethylallyl diphosphate
CC biosynthesis; dimethylallyl diphosphate from (2E)-4-hydroxy-3-
CC methylbutenyl diphosphate: step 1/1. {ECO:0000269|PubMed:16289098}.
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC phosphate: step 6/6. {ECO:0000269|PubMed:16289098}.
CC -!- SUBUNIT: Interacts with Fd/ferredoxin. {ECO:0000269|PubMed:16289098}.
CC -!- SUBCELLULAR LOCATION: Plastid, apicoplast {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the IspH family. {ECO:0000305}.
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DR EMBL; AF323927; AAK12102.1; -; Genomic_DNA.
DR EMBL; AL844501; CAD49005.1; -; Genomic_DNA.
DR RefSeq; XP_001350977.1; XM_001350941.1.
DR PDB; 4N7B; X-ray; 2.20 A; A=1-535.
DR PDBsum; 4N7B; -.
DR AlphaFoldDB; Q8I295; -.
DR SMR; Q8I295; -.
DR STRING; 5833.PFA0225w; -.
DR PRIDE; Q8I295; -.
DR EnsemblProtists; CAD49005; CAD49005; PF3D7_0104400.
DR GeneID; 813182; -.
DR KEGG; pfa:PF3D7_0104400; -.
DR VEuPathDB; PlasmoDB:PF3D7_0104400; -.
DR VEuPathDB; PlasmoDB:Pf7G8_010008600; -.
DR VEuPathDB; PlasmoDB:PfCD01_010008900; -.
DR VEuPathDB; PlasmoDB:PfDd2_010008200; -.
DR VEuPathDB; PlasmoDB:PfGA01_010008800; -.
DR VEuPathDB; PlasmoDB:PfGB4_010008700; -.
DR VEuPathDB; PlasmoDB:PfGN01_010008900; -.
DR VEuPathDB; PlasmoDB:PfHB3_010008600; -.
DR VEuPathDB; PlasmoDB:PfIT_010007900; -.
DR VEuPathDB; PlasmoDB:PfKE01_010007700; -.
DR VEuPathDB; PlasmoDB:PfKH01_010009600; -.
DR VEuPathDB; PlasmoDB:PfKH02_010008300; -.
DR VEuPathDB; PlasmoDB:PfML01_010008400; -.
DR VEuPathDB; PlasmoDB:PfSD01_010008100; -.
DR VEuPathDB; PlasmoDB:PfSN01_010007300; -.
DR VEuPathDB; PlasmoDB:PfTG01_010009500; -.
DR HOGENOM; CLU_038222_0_0_1; -.
DR InParanoid; Q8I295; -.
DR PhylomeDB; Q8I295; -.
DR BRENDA; 1.17.7.4; 4889.
DR UniPathway; UPA00056; UER00097.
DR UniPathway; UPA00059; UER00105.
DR Proteomes; UP000001450; Chromosome 1.
DR GO; GO:0020011; C:apicoplast; IDA:GeneDB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0051745; F:4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase activity; IDA:GeneDB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0050992; P:dimethylallyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IDA:GeneDB.
DR GO; GO:0010322; P:regulation of isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IDA:UniProtKB.
DR CDD; cd13944; lytB_ispH; 1.
DR HAMAP; MF_00191; IspH; 1.
DR InterPro; IPR003451; LytB/IspH.
DR PANTHER; PTHR30426; PTHR30426; 1.
DR Pfam; PF02401; LYTB; 1.
DR TIGRFAMs; TIGR00216; ispH_lytB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Apicoplast; Iron; Iron-sulfur; Isoprene biosynthesis;
KW Metal-binding; Oxidoreductase; Plastid; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Apicoplast"
FT /evidence="ECO:0000305"
FT CHAIN ?..535
FT /note="4-hydroxy-3-methylbut-2-enyl diphosphate reductase,
FT apicoplast"
FT /id="PRO_0000452697"
FT ACT_SITE 345
FT /note="Proton donor"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 231
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:24188825,
FT ECO:0007744|PDB:4N7B"
FT BINDING 260
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 293
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 315
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:24188825,
FT ECO:0007744|PDB:4N7B"
FT BINDING 343
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 383
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 413
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:24188825,
FT ECO:0007744|PDB:4N7B"
FT BINDING 441..443
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT BINDING 485
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P62623"
FT CONFLICT 526
FT /note="L -> F (in Ref. 1; AAK12102)"
FT /evidence="ECO:0000305"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 232..247
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 258..260
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 262..271
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 297..305
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 309..312
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 316..329
FT /evidence="ECO:0007829|PDB:4N7B"
FT TURN 330..332
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 334..339
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 344..350
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 357..362
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 363..368
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 387..400
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 414..427
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 431..437
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 442..452
FT /evidence="ECO:0007829|PDB:4N7B"
FT TURN 453..455
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 458..463
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 464..466
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 469..472
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 477..482
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 488..499
FT /evidence="ECO:0007829|PDB:4N7B"
FT TURN 501..503
FT /evidence="ECO:0007829|PDB:4N7B"
FT STRAND 506..511
FT /evidence="ECO:0007829|PDB:4N7B"
FT HELIX 524..533
FT /evidence="ECO:0007829|PDB:4N7B"
SQ SEQUENCE 535 AA; 62470 MW; E7CE6FCCD22FA07E CRC64;
MSVTTFCSLK KTDKCNIYIS KRAFSVFLFY LFFFLFFHFY FLCSSSFAVI IHESEKRKNI
MRRKRSILQI FENSIKSKEG KCNFTKRYIT HYYNIPLKIK KHDLPSVIKY FSHKPNGKHN
YVTNMITQKN RKSFLFFFFL YNKYFFGKQE QIRKMNYHEE MNKINIKNDG NRKIYMYPKN
DIHEEDGDHK NDVEINQKRN EQNCKSFNDE KNENARDPNK ILYLINPRGF CKGVSRAIET
VEECLKLFKP PIYVKHKIVH NDIVCKKLEK EGAIFIEDLN DVPDGHILIY SAHGISPQIR
EIAKKKKLIE IDATCPLVNK VHVYVQMKAK ENYDIILIGY KNHVEVIGTY NEAPHCTHIV
ENVNDVDKLN FPLNKKLFYV TQTTLSMDDC ALIVQKLKNK FPHIETIPSG SICYATTNRQ
TALNKICTKC DLTIVVGSSS SSNAKKLVYS SQIRNVPAVL LNTVHDLDQQ ILKNVNKIAL
TSAASTPEQE TQKFVNLLTN PPFNYTLQNF DGAHENVPKW KLPKNLLHMI KEREK
