FPPS_MYCTU
ID FPPS_MYCTU Reviewed; 359 AA.
AC P9WKH1; L0TFH9; P0A5H8; Q50727;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=(2E,6E)-farnesyl diphosphate synthase;
DE Short=E,E-FPP synthase;
DE Short=FPP synthase;
DE EC=2.5.1.10 {ECO:0000269|PubMed:15060088};
GN OrderedLocusNames=Rv3398c; ORFNames=MTCY78.30;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION AS A FARNESYL DIPHOSPHATE SYNTHASE, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND COFACTOR.
RX PubMed=15060088; DOI=10.1194/jlr.m400047-jlr200;
RA Dhiman R.K., Schulbach M.C., Mahapatra S., Baulard A.R., Vissa V.,
RA Brennan P.J., Crick D.C.;
RT "Identification of a novel class of omega,E,E-farnesyl diphosphate synthase
RT from Mycobacterium tuberculosis.";
RL J. Lipid Res. 45:1140-1147(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Catalyzes the condensation of isopentenyl pyrophosphate (IPP)
CC with geranyl diphosphate (GPP) to yield (2E,6E)-farnesyl diphosphate
CC (E,E-FPP). May be used for squalene and possibly sterol biosynthesis.
CC {ECO:0000269|PubMed:15060088}.
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 Evidence={ECO:0000269|PubMed:15060088};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19362;
CC Evidence={ECO:0000269|PubMed:15060088};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:15060088, ECO:0000305};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15060088, ECO:0000305};
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:15060088, ECO:0000305};
CC Note=Binds 2 Mg(2+) ions per subunit. Mn(2+) and Fe(2+) ions also
CC support activity. {ECO:0000269|PubMed:15060088, ECO:0000305};
CC -!- ACTIVITY REGULATION: Dithiothreitol increases the enzyme activity by
CC 2.5-fold.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.8 uM for IPP (at 37 degrees Celsius and pH 7.9)
CC {ECO:0000269|PubMed:15060088};
CC KM=43 uM for GPP (at 37 degrees Celsius and pH 7.9)
CC {ECO:0000269|PubMed:15060088};
CC Vmax=2.8 pmol/min/mg enzyme with GPP as substrate (at 37 degrees
CC Celsius and pH 7.9) {ECO:0000269|PubMed:15060088};
CC Vmax=6.7 pmol/min/mg enzyme with IPP as substrate (at 37 degrees
CC Celsius and pH 7.9) {ECO:0000269|PubMed:15060088};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:15060088};
CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis;
CC farnesyl diphosphate from geranyl diphosphate and isopentenyl
CC diphosphate. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15060088}.
CC -!- MISCELLANEOUS: This enzyme is unique in that it is the first reported
CC eubacterial E,E-FPP synthase that does not have four amino acids
CC between the aspartate residues of the first aspartate-rich motif (FARM)
CC and that has the features of the archaeal chain length-determining
CC (CLD) region.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46220.1; -; Genomic_DNA.
DR PIR; C70735; C70735.
DR RefSeq; WP_003417957.1; NZ_NVQJ01000027.1.
DR RefSeq; YP_177970.1; NC_000962.3.
DR AlphaFoldDB; P9WKH1; -.
DR SMR; P9WKH1; -.
DR STRING; 83332.Rv3398c; -.
DR SwissLipids; SLP:000001317; -.
DR PaxDb; P9WKH1; -.
DR DNASU; 887919; -.
DR GeneID; 887919; -.
DR KEGG; mtu:Rv3398c; -.
DR TubercuList; Rv3398c; -.
DR eggNOG; COG0142; Bacteria.
DR OMA; ISYEHRD; -.
DR PhylomeDB; P9WKH1; -.
DR BioCyc; MetaCyc:G185E-7675-MON; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004161; F:dimethylallyltranstransferase activity; IDA:MTBBASE.
DR GO; GO:0004337; F:geranyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0004659; F:prenyltransferase activity; IBA:GO_Central.
DR GO; GO:0045337; P:farnesyl diphosphate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0033384; P:geranyl diphosphate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0033386; P:geranylgeranyl diphosphate biosynthetic process; IDA:MTBBASE.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 1.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..359
FT /note="(2E,6E)-farnesyl diphosphate synthase"
FT /id="PRO_0000123968"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 112..116
FT /note="DDXXD motif"
FT /evidence="ECO:0000305"
FT MOTIF 242..246
FT /note="DDXXD motif"
FT /evidence="ECO:0000305"
FT BINDING 73
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 76
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 105
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 112
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 112
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 116
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 116
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 121
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
FT BINDING 122
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 201
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
FT BINDING 239
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="(2E)-geranyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58057"
FT /evidence="ECO:0000250"
SQ SEQUENCE 359 AA; 38852 MW; F59F229B19432E6E CRC64;
MRGTDEKYGL PPQPDSDRMT RRTLPVLGLA HELITPTLRQ MADRLDPHMR PVVSYHLGWS
DERGRPVNNN CGKAIRPALV FVAAEAAGAD PHSAIPGAVS VELVHNFSLV HDDLMDRDEH
RRHRPTVWAL WGDAMALLAG DAMLSLAHEV LLDCDSPHVG AALRAISEAT RELIRGQAAD
TAFESRTDVA LDECLKMAEG KTAALMAASA EVGALLAGAP RSVREALVAY GRHIGLAFQL
VDDLLGIWGR PEITGKPVYS DLRSRKKTLP VTWTVAHGGS AGRRLAAWLV DETGSQTASD
DELAAVAELI ECGGGRRWAS AEARRHVTQG IDMVARIGIP DRPAAELQDL AHYIVDRQA
