DXR_PLAFX
ID DXR_PLAFX Reviewed; 488 AA.
AC O96693;
DT 22-FEB-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=1-deoxy-D-xylulose 5-phosphate reductoisomerase, apicoplastic;
DE Short=1-deoxyxylulose-5-phosphate reductoisomerase;
DE Short=DOXP reductoisomerase;
DE Short=DXP reductoisomerase;
DE EC=1.1.1.267 {ECO:0000269|PubMed:10477522};
DE Flags: Precursor;
GN Name=DXR;
OS Plasmodium falciparum (isolate HB3).
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=137071;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY
RP REGULATION, PATHWAY, AND SUBCELLULAR LOCATION.
RC STRAIN=HB3;
RX PubMed=10477522; DOI=10.1126/science.285.5433.1573;
RA Jomaa H., Wiesner J., Sanderbrand S., Altincicek B., Weidemeyer C.,
RA Hintz M., Turbachova I., Eberl M., Zeidler J., Lichtenthaler H.K.,
RA Soldati D., Beck E.;
RT "Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as
RT antimalarial drugs.";
RL Science 285:1573-1576(1999).
RN [2] {ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9, ECO:0007744|PDB:3AUA}
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) IN COMPLEXES WITH NADPH;
RP FOSMIDOMYCIN DERIVATIVE FR900098; MAGNESIUM AND MANGANESE, COFACTOR, AND
RP SUBUNIT.
RC STRAIN=FCR-3 {ECO:0000269|PubMed:22355528};
RX PubMed=22355528; DOI=10.1038/srep00009;
RA Umeda T., Tanaka N., Kusakabe Y., Nakanishi M., Kitade Y., Nakamura K.T.;
RT "Molecular basis of fosmidomycin's action on the human malaria parasite
RT Plasmodium falciparum.";
RL Sci. Rep. 1:9-9(2011).
CC -!- FUNCTION: Catalyzes the NADP-dependent rearrangement and reduction of
CC 1-deoxy-D-xylulose-5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-
CC phosphate (MEP). {ECO:0000269|PubMed:10477522}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-C-methyl-D-erythritol 4-phosphate + NADP(+) = 1-deoxy-D-
CC xylulose 5-phosphate + H(+) + NADPH; Xref=Rhea:RHEA:13717,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57783, ChEBI:CHEBI:57792,
CC ChEBI:CHEBI:58262, ChEBI:CHEBI:58349; EC=1.1.1.267;
CC Evidence={ECO:0000269|PubMed:10477522};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:13719;
CC Evidence={ECO:0000305|PubMed:10477522};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22355528};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:22355528};
CC Note=Binds 1 divalent cation per subunit. Mg(2+) or Mn(2+).
CC {ECO:0000269|PubMed:22355528};
CC -!- ACTIVITY REGULATION: Inhibited by fosmidomycin and its derivative
CC FT900098. {ECO:0000269|PubMed:10477522}.
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC phosphate: step 1/6. {ECO:0000305|PubMed:10477522}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:22355528}.
CC -!- SUBCELLULAR LOCATION: Plastid, apicoplast
CC {ECO:0000269|PubMed:10477522}.
CC -!- SIMILARITY: Belongs to the DXR family. {ECO:0000305}.
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DR EMBL; AF111813; AAD03739.1; -; Genomic_DNA.
DR PDB; 3AU8; X-ray; 1.86 A; A/B=1-488.
DR PDB; 3AU9; X-ray; 1.90 A; A/B=1-488.
DR PDB; 3AUA; X-ray; 2.15 A; A/B=1-488.
DR PDB; 3WQQ; X-ray; 2.25 A; A/B=1-488.
DR PDB; 3WQR; X-ray; 1.97 A; A/B=1-488.
DR PDB; 3WQS; X-ray; 2.35 A; B=1-488.
DR PDB; 4GAE; X-ray; 2.30 A; A/B=75-488.
DR PDB; 4KP7; X-ray; 2.00 A; A/B=74-488.
DR PDBsum; 3AU8; -.
DR PDBsum; 3AU9; -.
DR PDBsum; 3AUA; -.
DR PDBsum; 3WQQ; -.
DR PDBsum; 3WQR; -.
DR PDBsum; 3WQS; -.
DR PDBsum; 4GAE; -.
DR PDBsum; 4KP7; -.
DR AlphaFoldDB; O96693; -.
DR SMR; O96693; -.
DR VEuPathDB; PlasmoDB:PfHB3_140072900; -.
DR BioCyc; MetaCyc:MON-18397; -.
DR BRENDA; 1.1.1.267; 4889.
DR UniPathway; UPA00056; UER00092.
DR EvolutionaryTrace; O96693; -.
DR GO; GO:0020011; C:apicoplast; IEA:UniProtKB-SubCell.
DR GO; GO:0030604; F:1-deoxy-D-xylulose-5-phosphate reductoisomerase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070402; F:NADPH binding; IEA:InterPro.
DR GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IEA:UniProtKB-UniPathway.
DR HAMAP; MF_00183; DXP_reductoisom; 1.
DR InterPro; IPR003821; DXP_reductoisomerase.
DR InterPro; IPR013644; DXP_reductoisomerase_C.
DR InterPro; IPR013512; DXP_reductoisomerase_N.
DR InterPro; IPR026877; DXPR_C.
DR InterPro; IPR036169; DXPR_C_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR30525; PTHR30525; 1.
DR Pfam; PF08436; DXP_redisom_C; 1.
DR Pfam; PF02670; DXP_reductoisom; 1.
DR Pfam; PF13288; DXPR_C; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF69055; SSF69055; 1.
DR TIGRFAMs; TIGR00243; Dxr; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apicoplast; Isoprene biosynthesis; Magnesium; Manganese;
KW Metal-binding; NADP; Oxidoreductase; Plastid; Transit peptide.
FT TRANSIT 1..72
FT /note="Apicoplast"
FT /evidence="ECO:0000305"
FT CHAIN 73..488
FT /note="1-deoxy-D-xylulose 5-phosphate reductoisomerase,
FT apicoplastic"
FT /id="PRO_0000415608"
FT REGION 306..312
FT /note="Binding to substrate phosphate group"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 86..89
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9,
FT ECO:0007744|PDB:3AUA"
FT BINDING 115..117
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9,
FT ECO:0007744|PDB:3AUA"
FT BINDING 205
FT /ligand="1-deoxy-D-xylulose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:57792"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 206
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU9, ECO:0007744|PDB:3AUA"
FT BINDING 231
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9,
FT ECO:0007744|PDB:3AUA"
FT BINDING 233
FT /ligand="1-deoxy-D-xylulose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:57792"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 233
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9,
FT ECO:0007744|PDB:3AUA"
FT BINDING 270
FT /ligand="1-deoxy-D-xylulose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:57792"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 293
FT /ligand="1-deoxy-D-xylulose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:57792"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 299
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU9, ECO:0007744|PDB:3AUA"
FT BINDING 315
FT /ligand="1-deoxy-D-xylulose 5-phosphate"
FT /ligand_id="ChEBI:CHEBI:57792"
FT /evidence="ECO:0000250|UniProtKB:P45568"
FT BINDING 315
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:22355528,
FT ECO:0007744|PDB:3AU8, ECO:0007744|PDB:3AU9,
FT ECO:0007744|PDB:3AUA"
FT STRAND 78..84
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 88..103
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 107..116
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 118..128
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 147..150
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:3WQS"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 161..170
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 176..179
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 183..195
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 199..202
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 206..221
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 243..246
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 251..253
FT /evidence="ECO:0007829|PDB:4GAE"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 262..269
FT /evidence="ECO:0007829|PDB:3AU8"
FT TURN 273..276
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 279..282
FT /evidence="ECO:0007829|PDB:3AU8"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 301..307
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 310..323
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 330..334
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 340..346
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 351..355
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 361..369
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 383..386
FT /evidence="ECO:0007829|PDB:3AU8"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:3AU8"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 400..411
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 415..431
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 437..450
FT /evidence="ECO:0007829|PDB:3AU8"
FT HELIX 460..483
FT /evidence="ECO:0007829|PDB:3AU8"
SQ SEQUENCE 488 AA; 55757 MW; 4E280C81CDFAD3EF CRC64;
MKKYIYIYFF FITITINDLV INNTSKCVSI ERRKNNAYIN YGIGYNGPDN KITKSRRCKR
IKLCKKDLID IGAIKKPINV AIFGSTGSIG TNALNIIREC NKIENVFNVK ALYVNKSVNE
LYEQAREFLP EYLCIHDKSV YEELKELVKN IKDYKPIILC GDEGMKEICS SNSIDKIVIG
IDSFQGLYST MYAIMNNKIV ALANKESIVS AGFFLKKLLN IHKNAKIIPV DSEHSAIFQC
LDNNKVLKTK CLQDNFSKIN NINKIFLCSS GGPFQNLTMD ELKNVTSENA LKHPKWKMGK
KITIDSATMM NKGLEVIETH FLFDVDYNDI EVIVHKECII HSCVEFIDKS VISQMYYPDM
QIPILYSLTW PDRIKTNLKP LDLAQVSTLT FHKPSLEHFP CIKLAYQAGI KGNFYPTVLN
ASNEIANNLF LNNKIKYFDI SSIISQVLES FNSQKVSENS EDLMKQILQI HSWAKDKATD
IYNKHNSS
