ID   ISPA_ECOLI              Reviewed;         299 AA.
AC   P22939; Q2MC05;
DT   01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1991, sequence version 1.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Farnesyl diphosphate synthase;
DE            Short=FPP synthase;
DE            EC=2.5.1.10;
DE   AltName: Full=(2E,6E)-farnesyl diphosphate synthase;
DE   AltName: Full=Geranyltranstransferase;
GN   Name=ispA; OrderedLocusNames=b0421, JW0411;
OS   Escherichia coli (strain K12).
OC   Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC   Enterobacteriaceae; Escherichia.
OX   NCBI_TaxID=83333;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=K12;
RX   PubMed=2089044; DOI=10.1093/oxfordjournals.jbchem.a123327;
RA   Fujisaki S., Hara H., Nishimura Y., Horiuchi K., Nishino T.;
RT   "Cloning and nucleotide sequence of the ispA gene responsible for farnesyl
RT   diphosphate synthase activity in Escherichia coli.";
RL   J. Biochem. 108:995-1000(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RA   Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA   Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA   Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT   "Sequence of minutes 4-25 of Escherichia coli.";
RL   Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / MG1655 / ATCC 47076;
RX   PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA   Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA   Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA   Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA   Shao Y.;
RT   "The complete genome sequence of Escherichia coli K-12.";
RL   Science 277:1453-1462(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX   PubMed=16738553; DOI=10.1038/msb4100049;
RA   Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA   Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT   "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT   and W3110.";
RL   Mol. Syst. Biol. 2:E1-E5(2006).
RN   [5]
RP   X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH MAGNESIUM;
RP   ISOPENTENYL DIPHOSPHATE AND DIMETHYLALLYL S-THIOLODIPHOSPHATE, SUBUNIT, AND
RP   COFACTOR.
RX   PubMed=14672944; DOI=10.1074/jbc.c300511200;
RA   Hosfield D.J., Zhang Y., Dougan D.R., Broun A., Tari L.W., Swanson R.V.,
RA   Finn J.;
RT   "Structural basis for bisphosphonate-mediated inhibition of isoprenoid
RT   biosynthesis.";
RL   J. Biol. Chem. 279:8526-8529(2004).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-
CC         farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769,
CC         ChEBI:CHEBI:175763; EC=2.5.1.10;
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:14672944};
CC       Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000269|PubMed:14672944};
CC   -!- INTERACTION:
CC       P22939; P77609: flxA; NbExp=6; IntAct=EBI-553011, EBI-553024;
CC       P22939; P33221: purT; NbExp=4; IntAct=EBI-553011, EBI-553029;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; D00694; BAA00599.1; -; Genomic_DNA.
DR   EMBL; U82664; AAB40177.1; -; Genomic_DNA.
DR   EMBL; U00096; AAC73524.1; -; Genomic_DNA.
DR   EMBL; AP009048; BAE76201.1; -; Genomic_DNA.
DR   PIR; JQ0665; JQ0665.
DR   RefSeq; NP_414955.1; NC_000913.3.
DR   RefSeq; WP_000347217.1; NZ_SSZK01000009.1.
DR   PDB; 1RQI; X-ray; 2.42 A; A/B=1-299.
DR   PDB; 1RQJ; X-ray; 1.95 A; A/B=1-299.
DR   PDBsum; 1RQI; -.
DR   PDBsum; 1RQJ; -.
DR   AlphaFoldDB; P22939; -.
DR   SMR; P22939; -.
DR   BioGRID; 4259837; 475.
DR   BioGRID; 849453; 3.
DR   DIP; DIP-10044N; -.
DR   IntAct; P22939; 16.
DR   STRING; 511145.b0421; -.
DR   BindingDB; P22939; -.
DR   ChEMBL; CHEMBL1075078; -.
DR   DrugBank; DB02270; Dimethylallyl S-Thiolodiphosphate.
DR   DrugBank; DB02508; Isopentyl Pyrophosphate.
DR   DrugBank; DB04160; Pyrophosphoric acid.
DR   DrugCentral; P22939; -.
DR   jPOST; P22939; -.
DR   PaxDb; 511145-b0421; -.
DR   EnsemblBacteria; AAC73524; AAC73524; b0421.
DR   GeneID; 945064; -.
DR   KEGG; ecj:JW0411; -.
DR   KEGG; eco:b0421; -.
DR   PATRIC; fig|1411691.4.peg.1856; -.
DR   EchoBASE; EB0503; -.
DR   eggNOG; COG0142; Bacteria.
DR   HOGENOM; CLU_014015_0_1_6; -.
DR   InParanoid; P22939; -.
DR   OMA; EGMIGGQ; -.
DR   OrthoDB; 9805316at2; -.
DR   PhylomeDB; P22939; -.
DR   BioCyc; EcoCyc:FPPSYN-MONOMER; -.
DR   BioCyc; MetaCyc:FPPSYN-MONOMER; -.
DR   BRENDA; 2.5.1.10; 2026.
DR   SABIO-RK; P22939; -.
DR   EvolutionaryTrace; P22939; -.
DR   PRO; PR:P22939; -.
DR   Proteomes; UP000000318; Chromosome.
DR   Proteomes; UP000000625; Chromosome.
DR   GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR   GO; GO:0004161; F:dimethylallyltranstransferase activity; IDA:EcoCyc.
DR   GO; GO:0004337; F:geranyltranstransferase activity; IDA:EcoCyc.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004659; F:prenyltransferase activity; IBA:GO_Central.
DR   GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; IMP:EcoCyc.
DR   GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IMP:EcoCyc.
DR   CDD; cd00685; Trans_IPPS_HT; 1.
DR   Gene3D; 1.10.600.10; Farnesyl Diphosphate Synthase; 1.
DR   InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR   InterPro; IPR000092; Polyprenyl_synt.
DR   InterPro; IPR033749; Polyprenyl_synt_CS.
DR   PANTHER; PTHR43281; FARNESYL DIPHOSPHATE SYNTHASE; 1.
DR   PANTHER; PTHR43281:SF1; FARNESYL DIPHOSPHATE SYNTHASE; 1.
DR   Pfam; PF00348; polyprenyl_synt; 1.
DR   SFLD; SFLDS00005; Isoprenoid_Synthase_Type_I; 1.
DR   SFLD; SFLDG01017; Polyprenyl_Transferase_Like; 1.
DR   SUPFAM; SSF48576; Terpenoid synthases; 1.
DR   PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR   PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
DR   SWISS-2DPAGE; P22939; -.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Isoprene biosynthesis; Magnesium; Metal-binding;
KW   Reference proteome; Transferase.
FT   CHAIN           1..299
FT                   /note="Farnesyl diphosphate synthase"
FT                   /id="PRO_0000123982"
FT   BINDING         45
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         48
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         77
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         84
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         84
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         90
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         90
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         95
FT                   /ligand="(2E)-geranyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58057"
FT   BINDING         96
FT                   /ligand="isopentenyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:128769"
FT                   /evidence="ECO:0000269|PubMed:14672944"
FT   BINDING         181
FT                   /ligand="(2E)-geranyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58057"
FT   BINDING         182
FT                   /ligand="(2E)-geranyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58057"
FT   BINDING         220
FT                   /ligand="(2E)-geranyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58057"
FT   BINDING         237
FT                   /ligand="(2E)-geranyl diphosphate"
FT                   /ligand_id="ChEBI:CHEBI:58057"
FT   HELIX           3..22
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   STRAND          25..27
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           31..41
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           47..58
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           63..84
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   TURN            87..90
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           101..105
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           107..127
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           135..149
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           154..163
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   TURN            164..167
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           171..181
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           183..195
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   TURN            196..198
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           199..229
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           232..235
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           241..245
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           250..254
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           256..278
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   TURN            279..281
FT                   /evidence="ECO:0007829|PDB:1RQJ"
FT   HELIX           285..296
FT                   /evidence="ECO:0007829|PDB:1RQJ"
SQ   SEQUENCE   299 AA;  32160 MW;  15BADD5E135060CA CRC64;
     MDFPQQLEAC VKQANQALSR FIAPLPFQNT PVVETMQYGA LLGGKRLRPF LVYATGHMFG
     VSTNTLDAPA AAVECIHAYS LIHDDLPAMD DDDLRRGLPT CHVKFGEANA ILAGDALQTL
     AFSILSDADM PEVSDRDRIS MISELASASG IAGMCGGQAL DLDAEGKHVP LDALERIHRH
     KTGALIRAAV RLGALSAGDK GRRALPVLDK YAESIGLAFQ VQDDILDVVG DTATLGKRQG
     ADQQLGKSTY PALLGLEQAR KKARDLIDDA RQSLKQLAEQ SLDTSALEAL ADYIIQRNK
//