ZFPP_MYCTU
ID ZFPP_MYCTU Reviewed; 262 AA.
AC P9WFF5; L0T8K3; O53434;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=(2Z,6E)-farnesyl diphosphate synthase;
DE EC=2.5.1.68;
DE AltName: Full=Short-chain Z-isoprenyl diphosphate synthase;
DE AltName: Full=Z-FPP synthase;
DE Short=Z-FPPS;
DE AltName: Full=Z-Polyprenyl diphosphate synthase;
DE AltName: Full=Z-isoprenyl diphosphate synthase;
GN OrderedLocusNames=Rv1086; ORFNames=MTV017.39;
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, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11004176; DOI=10.1128/jb.182.20.5771-5778.2000;
RA Crick D.C., Schulbach M.C., Zink E.E., Macchia M., Barontini S.,
RA Besra G.S., Brennan P.J.;
RT "Polyprenyl phosphate biosynthesis in Mycobacterium tuberculosis and
RT Mycobacterium smegmatis.";
RL J. Bacteriol. 182:5771-5778(2000).
RN [3]
RP FUNCTION AS A FARNESYL DIPHOSPHATE SYNTHASE.
RX PubMed=10816587; DOI=10.1074/jbc.m003194200;
RA Schulbach M.C., Brennan P.J., Crick D.C.;
RT "Identification of a short (C15) chain Z-isoprenyl diphosphate synthase and
RT a homologous long (C50) chain isoprenyl diphosphate synthase in
RT Mycobacterium tuberculosis.";
RL J. Biol. Chem. 275:22876-22881(2000).
RN [4]
RP FUNCTION AS FARNESYL DIPHOSPHATE SYNTHASE, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVITY REGULATION, AND COFACTOR.
RX PubMed=11152452; DOI=10.1074/jbc.m007168200;
RA Schulbach M.C., Mahapatra S., Macchia M., Barontini S., Papi C.,
RA Minutolo F., Bertini S., Brennan P.J., Crick D.C.;
RT "Purification, enzymatic characterization, and inhibition of the Z-farnesyl
RT diphosphate synthase from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 276:11624-11630(2001).
RN [5]
RP MUTAGENESIS OF LEU-84.
RX PubMed=18790692; DOI=10.1016/j.bbrc.2008.09.014;
RA Noike M., Ambo T., Kikuchi S., Suzuki T., Yamashita S., Takahashi S.,
RA Kurokawa H., Mahapatra S., Crick D.C., Koyama T.;
RT "Product chain-length determination mechanism of Z,E-farnesyl diphosphate
RT synthase.";
RL Biochem. Biophys. Res. Commun. 377:17-22(2008).
RN [6]
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).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 30-256, MUTAGENESIS OF LEU-84 AND
RP VAL-107, AND SUBUNIT.
RX PubMed=18597781; DOI=10.1016/j.jmb.2008.05.060;
RA Wang W., Dong C., McNeil M., Kaur D., Mahapatra S., Crick D.C.,
RA Naismith J.H.;
RT "The structural basis of chain length control in Rv1086.";
RL J. Mol. Biol. 381:129-140(2008).
CC -!- FUNCTION: Catalyzes the condensation of only one isopentenyl
CC pyrophosphate (IPP) unit in the cis configuration to E-geranyl
CC diphosphate (E-GPP) generating the 15 carbon product (2Z,6E)-farnesyl
CC diphosphate (Z-FPP or EZ-FPP). Z-FPP is the precursor of decaprenyl
CC diphosphate, which has a central role in the biosynthesis of the
CC mycobacterial cell wall. {ECO:0000269|PubMed:10816587,
CC ECO:0000269|PubMed:11004176, ECO:0000269|PubMed:11152452}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2Z,6E)-
CC farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:23300,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769,
CC ChEBI:CHEBI:162247; EC=2.5.1.68;
CC Evidence={ECO:0000269|PubMed:11004176};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11152452};
CC Note=Binds 2 magnesium ions per subunit. {ECO:0000269|PubMed:11152452};
CC -!- ACTIVITY REGULATION: Inhibited by citronellyl diphosphate.
CC {ECO:0000269|PubMed:11152452}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=16 uM for neryl diphosphate (at pH 7.9 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:11152452};
CC KM=38 uM for E-GPP (at pH 7.9 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:11152452};
CC KM=124 uM for IPP (at pH 7.9 and 37 degrees Celsius)
CC {ECO:0000269|PubMed:11152452};
CC Vmax=4328 pmol/min/mg enzyme for IPP (at pH 7.9 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:11152452};
CC Vmax=2827 pmol/min/mg enzyme for E-GPP (at pH 7.9 and 37 degrees
CC Celsius) {ECO:0000269|PubMed:11152452};
CC Vmax=1098 pmol/min/mg enzyme for neryl diphosphate (at pH 7.9 and 37
CC degrees Celsius) {ECO:0000269|PubMed:11152452};
CC pH dependence:
CC Optimum pH is between 7 and 8. {ECO:0000269|PubMed:11152452};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:18597781}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11004176}. Cell
CC membrane {ECO:0000269|PubMed:11004176}.
CC -!- SIMILARITY: Belongs to the UPP synthase family. Z-FPP synthase
CC subfamily. {ECO:0000305}.
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DR EMBL; AL123456; CCP43837.1; -; Genomic_DNA.
DR PIR; D70895; D70895.
DR RefSeq; NP_215602.1; NC_000962.3.
DR RefSeq; WP_003906511.1; NZ_NVQJ01000080.1.
DR PDB; 2VFW; X-ray; 2.30 A; A/B=30-256.
DR PDB; 2VG0; X-ray; 1.70 A; A/B=30-256.
DR PDB; 2VG1; X-ray; 1.70 A; A/B=29-256.
DR PDBsum; 2VFW; -.
DR PDBsum; 2VG0; -.
DR PDBsum; 2VG1; -.
DR AlphaFoldDB; P9WFF5; -.
DR SMR; P9WFF5; -.
DR STRING; 83332.Rv1086; -.
DR DrugBank; DB07780; Farnesyl diphosphate.
DR DrugBank; DB02552; Geranyl Diphosphate.
DR PaxDb; P9WFF5; -.
DR DNASU; 887097; -.
DR GeneID; 887097; -.
DR KEGG; mtu:Rv1086; -.
DR TubercuList; Rv1086; -.
DR eggNOG; COG0020; Bacteria.
DR OMA; TKGQPDP; -.
DR PhylomeDB; P9WFF5; -.
DR BioCyc; MetaCyc:G185E-5248-MON; -.
DR BRENDA; 2.5.1.68; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MTBBASE.
DR GO; GO:0008834; F:di-trans,poly-cis-decaprenylcistransferase activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0002094; F:polyprenyltransferase activity; IBA:GO_Central.
DR GO; GO:0033850; F:Z-farnesyl diphosphate synthase activity; IDA:UniProtKB.
DR GO; GO:0016094; P:polyprenol biosynthetic process; IDA:MTBBASE.
DR CDD; cd00475; Cis_IPPS; 1.
DR Gene3D; 3.40.1180.10; -; 1.
DR HAMAP; MF_01139; ISPT; 1.
DR InterPro; IPR001441; UPP_synth-like.
DR InterPro; IPR018520; UPP_synth-like_CS.
DR InterPro; IPR036424; UPP_synth-like_sf.
DR PANTHER; PTHR10291; PTHR10291; 1.
DR Pfam; PF01255; Prenyltransf; 1.
DR SUPFAM; SSF64005; SSF64005; 1.
DR TIGRFAMs; TIGR00055; uppS; 1.
DR PROSITE; PS01066; UPP_SYNTHASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Magnesium; Membrane; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..262
FT /note="(2Z,6E)-farnesyl diphosphate synthase"
FT /id="PRO_0000123748"
FT ACT_SITE 40
FT /evidence="ECO:0000250"
FT ACT_SITE 89
FT /note="Proton acceptor"
FT BINDING 40
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 41..44
FT /ligand="substrate"
FT BINDING 45
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 86..88
FT /ligand="substrate"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 211
FT /ligand="substrate"
FT BINDING 217..219
FT /ligand="substrate"
FT BINDING 230
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 84
FT /note="Important for determining product length"
FT MUTAGEN 84
FT /note="L->A: 4-fold decrease in affinity relative to the
FT wild-type and able to synthesize prenyl diphosphates
FT containing 20 and 50 carbon atoms when GPP and EE-FPP are
FT used as the allylic substrates, respectively, whereas the
FT wild-type enzyme generates product that is restricted to 15
FT carbon atoms with GPP as substrate and does not react with
FT EE-FPP; when associated with G-107."
FT /evidence="ECO:0000269|PubMed:18597781,
FT ECO:0000269|PubMed:18790692"
FT MUTAGEN 107
FT /note="V->G: No detectable activity. 4-fold decrease in
FT affinity relative to the wild-type and able to synthesize
FT prenyl diphosphates containing 20 and 50 carbon atoms when
FT GPP and EE-FPP are used as the allylic substrates,
FT respectively, whereas the wild-type enzyme generates
FT product that is restricted to 15 carbon atoms with GPP as
FT substrate and does not react with EE-FPP; when associated
FT with A-84."
FT /evidence="ECO:0000269|PubMed:18597781"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 42..48
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 55..75
FT /evidence="ECO:0007829|PDB:2VG0"
FT STRAND 78..86
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 88..91
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 94..111
FT /evidence="ECO:0007829|PDB:2VG0"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:2VG0"
FT STRAND 119..124
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 131..142
FT /evidence="ECO:0007829|PDB:2VG0"
FT STRAND 151..158
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 160..177
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 182..188
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 191..197
FT /evidence="ECO:0007829|PDB:2VG0"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:2VG0"
FT STRAND 207..211
FT /evidence="ECO:0007829|PDB:2VG0"
FT TURN 219..228
FT /evidence="ECO:0007829|PDB:2VG0"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:2VG0"
FT HELIX 243..255
FT /evidence="ECO:0007829|PDB:2VG0"
SQ SEQUENCE 262 AA; 29410 MW; 2D6745748FE22518 CRC64;
MEIIPPRLKE PLYRLYELRL RQGLAASKSD LPRHIAVLCD GNRRWARSAG YDDVSYGYRM
GAAKIAEMLR WCHEAGIELA TVYLLSTENL QRDPDELAAL IEIITDVVEE ICAPANHWSV
RTVGDLGLIG EEPARRLRGA VESTPEVASF HVNVAVGYGG RREIVDAVRA LLSKELANGA
TAEELVDAVT VEGISENLYT SGQPDPDLVI RTSGEQRLSG FLLWQSAYSE MWFTEAHWPA
FRHVDFLRAL RDYSARHRSY GR
