NPPPS_MYCTU
ID NPPPS_MYCTU Reviewed; 335 AA.
AC O06428; F2GMK7; I6X9B6; Q7D9M6;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Nonaprenyl diphosphate synthase {ECO:0000305};
DE EC=2.5.1.85 {ECO:0000269|PubMed:32495977};
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase {ECO:0000305};
DE Short=E,E-FPP synthase {ECO:0000305};
DE Short=FPP synthase {ECO:0000305};
DE EC=2.5.1.10 {ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:32495977};
DE AltName: Full=Geranylgeranyl diphosphate synthase {ECO:0000305};
DE Short=GGPP synthase {ECO:0000305};
DE Short=GGPS {ECO:0000305};
DE EC=2.5.1.29 {ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:30301210, ECO:0000269|PubMed:32495977};
GN Name=grcC1 {ECO:0000312|EMBL:CCP43300.1};
GN OrderedLocusNames=Rv0562 {ECO:0000312|EMBL:CCP43300.1};
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 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 [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23091471; DOI=10.3389/fmicb.2012.00368;
RA Mann F.M., Xu M., Davenport E.K., Peters R.J.;
RT "Functional characterization and evolution of the isotuberculosinol operon
RT in Mycobacterium tuberculosis and related Mycobacteria.";
RL Front. Microbiol. 3:368-368(2012).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF ASP-98 AND
RP ASP-223.
RX PubMed=30301210; DOI=10.3390/molecules23102546;
RA Nagel R., Thomas J.A., Adekunle F.A., Mann F.M., Peters R.J.;
RT "Arginine in the FARM and SARM: a role in chain-length determination for
RT arginine in the aspartate-rich motifs of isoprenyl diphosphate synthases
RT from Mycobacterium tuberculosis.";
RL Molecules 23:2546-2546(2018).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PATHWAY.
RX PubMed=32495977; DOI=10.1002/cbic.202000235;
RA Abe T., Ozaki S., Ueda D., Sato T.;
RT "Insight into isoprenoid biosynthesis by functional analysis of isoprenyl
RT diphosphate synthases from Mycobacterium vanbaalenii and Mycobacterium
RT tuberculosis.";
RL ChemBioChem 21:2931-2938(2020).
CC -!- FUNCTION: Catalyzes the sequential condensations of isopentenyl
CC pyrophosphate (IPP) with geranyl diphosphate (GPP) to yield (2E,6E)-
CC farnesyl diphosphate (E,E-FPP), with E,E-FPP to yield geranylgeranyl
CC diphosphate (GGPP) and with GGPP to yield nonaprenyl diphosphate
CC (PubMed:23091471, PubMed:30301210, PubMed:32495977). May also have weak
CC activity with dimethylallyl diphosphate (DMAPP) (PubMed:23091471).
CC {ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:30301210,
CC ECO:0000269|PubMed:32495977}.
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:23091471, ECO:0000269|PubMed:32495977};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19362;
CC Evidence={ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:32495977};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate =
CC (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate;
CC Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29;
CC Evidence={ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:30301210,
CC ECO:0000269|PubMed:32495977};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654;
CC Evidence={ECO:0000269|PubMed:23091471, ECO:0000269|PubMed:30301210,
CC ECO:0000269|PubMed:32495977};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E,10E)-geranylgeranyl diphosphate + 5 isopentenyl
CC diphosphate = all-trans-nonaprenyl diphosphate + 5 diphosphate;
CC Xref=Rhea:RHEA:27594, ChEBI:CHEBI:33019, ChEBI:CHEBI:58391,
CC ChEBI:CHEBI:58756, ChEBI:CHEBI:128769; EC=2.5.1.85;
CC Evidence={ECO:0000269|PubMed:32495977};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27595;
CC Evidence={ECO:0000269|PubMed:32495977};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:32495977};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.7 uM for IPP {ECO:0000269|PubMed:23091471};
CC KM=2.3 uM for GPP {ECO:0000269|PubMed:23091471};
CC KM=11 uM for FPP {ECO:0000269|PubMed:23091471};
CC KM=5 uM for DMAPP {ECO:0000269|PubMed:23091471};
CC Note=kcat is 0.3 min(-1) with GPP as substrate. kcat is 0.7 min(-1)
CC with FPP as substrate. kcat is 0.17 min(-1) with DMAPP as substrate.
CC {ECO:0000269|PubMed:23091471};
CC -!- PATHWAY: Isoprenoid biosynthesis; farnesyl diphosphate biosynthesis;
CC farnesyl diphosphate from geranyl diphosphate and isopentenyl
CC diphosphate. {ECO:0000269|PubMed:32495977}.
CC -!- PATHWAY: Isoprenoid biosynthesis; geranylgeranyl diphosphate
CC biosynthesis; geranylgeranyl diphosphate from farnesyl diphosphate and
CC isopentenyl diphosphate: step 1/1. {ECO:0000269|PubMed:32495977}.
CC -!- DOMAIN: Contains the canonical two aspartate-rich DDxxD motifs,
CC designated as FARM (the first aspartate-rich motif) and SARM (the
CC second aspartate-rich motif). The primary role of the FARM and SARM is
CC the chelation of the divalent magnesium ion cofactors that assist
CC substrate binding and catalysis, but it may also play a role in
CC determining product chain length. {ECO:0000305|PubMed:30301210}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43300.1; -; Genomic_DNA.
DR RefSeq; NP_215076.1; NC_000962.3.
DR RefSeq; WP_003402957.1; NZ_NVQJ01000036.1.
DR AlphaFoldDB; O06428; -.
DR SMR; O06428; -.
DR STRING; 83332.Rv0562; -.
DR PaxDb; O06428; -.
DR PRIDE; O06428; -.
DR DNASU; 887647; -.
DR GeneID; 45424526; -.
DR GeneID; 887647; -.
DR KEGG; mtu:Rv0562; -.
DR PATRIC; fig|83332.111.peg.619; -.
DR TubercuList; Rv0562; -.
DR eggNOG; COG0142; Bacteria.
DR OMA; CEGQALD; -.
DR PhylomeDB; O06428; -.
DR UniPathway; UPA00389; UER00564.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0052924; F:all-trans-nonaprenyl-diphosphate synthase (geranylgeranyl-diphosphate specific) activity; IEA:UniProtKB-EC.
DR GO; GO:0004311; F:farnesyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0004337; F:geranyltranstransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004659; F:prenyltransferase activity; IBA:GO_Central.
DR GO; GO:0033386; P:geranylgeranyl diphosphate biosynthetic process; IEA:UniProtKB-UniPathway.
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; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..335
FT /note="Nonaprenyl diphosphate synthase"
FT /id="PRO_0000451297"
FT MOTIF 97..101
FT /note="DDXXD motif"
FT /evidence="ECO:0000305|PubMed:30301210"
FT MOTIF 223..227
FT /note="DDXXD motif"
FT /evidence="ECO:0000305|PubMed:30301210"
FT BINDING 57
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 60
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 90
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 97
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 101
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 101
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 107
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 98
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000305|PubMed:30301210"
FT SITE 223
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000305|PubMed:30301210"
FT MUTAGEN 98
FT /note="D->R: Leads to the appearance of shorter chain
FT products, GPP and E,E-FPP, with only small amounts of GGPP
FT produced."
FT /evidence="ECO:0000269|PubMed:30301210"
FT MUTAGEN 223
FT /note="D->R: Leads to the appearance of shorter chain
FT products, GPP and E,E-FPP, with only small amounts of GGPP
FT produced."
FT /evidence="ECO:0000269|PubMed:30301210"
SQ SEQUENCE 335 AA; 35560 MW; F4D7BF4FEE9D832F CRC64;
MRTPATVVAG VDLGDAVFAA AVRAGVARVE QLMDTELRQA DEVMSDSLLH LFNAGGKRFR
PLFTVLSAQI GPQPDAAAVT VAGAVIEMIH LATLYHDDVM DEAQVRRGAP SANAQWGNNV
AILAGDYLLA TASRLVARLG PEAVRIIADT FAQLVTGQMR ETRGTSENVD SIEQYLKVVQ
EKTGSLIGAA GRLGGMFSGA TDEQVERLSR LGGVVGTAFQ IADDIIDIDS ESDESGKLPG
TDVREGVHTL PMLYALRESG PDCARLRALL NGPVDDDAEV REALTLLRAS PGMARAKDVL
AQYAAQARHE LALLPDVPGR RALAALVDYT VSRHG
