GPPS_MYCTU
ID GPPS_MYCTU Reviewed; 325 AA.
AC O05572; I6XWR7; L0T701;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=Dimethylallyltranstransferase {ECO:0000305};
DE EC=2.5.1.1 {ECO:0000269|PubMed:21237161, ECO:0000269|PubMed:30301210};
DE AltName: Full=Geranyl diphosphate synthase {ECO:0000303|PubMed:21237161};
DE Short=GPP synthase {ECO:0000303|PubMed:21237161};
GN Name=grcC2 {ECO:0000312|EMBL:CCP43739.1};
GN OrderedLocusNames=Rv0989c {ECO:0000312|EMBL:CCP43739.1};
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 FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16586367; DOI=10.1086/502631;
RA Jain S.K., Paul-Satyaseela M., Lamichhane G., Kim K.S., Bishai W.R.;
RT "Mycobacterium tuberculosis invasion and traversal across an in vitro human
RT blood-brain barrier as a pathogenic mechanism for central nervous system
RT tuberculosis.";
RL J. Infect. Dis. 193:1287-1295(2006).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21237161; DOI=10.1016/j.febslet.2011.01.007;
RA Mann F.M., Thomas J.A., Peters R.J.;
RT "Rv0989c encodes a novel (E)-geranyl diphosphate synthase facilitating
RT decaprenyl diphosphate biosynthesis in Mycobacterium tuberculosis.";
RL FEBS Lett. 585:549-554(2011).
RN [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF ARG-92 AND
RP ARG-217.
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).
CC -!- FUNCTION: Catalyzes the addition of isopentenyl diphosphate (IPP) onto
CC dimethylallyl diphosphate (DMAPP) to form geranyl pyrophosphate (GPP)
CC (PubMed:21237161, PubMed:30301210). Is probably involved in the
CC biosynthesis of decaprenyl diphosphate, which is required for
CC mycobacterial cell wall synthesis (PubMed:21237161). Could be required
CC for host endothelial-cell invasion and/or intracellular survival
CC (PubMed:16586367). {ECO:0000269|PubMed:16586367,
CC ECO:0000269|PubMed:21237161, ECO:0000269|PubMed:30301210}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-
CC geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057,
CC ChEBI:CHEBI:128769; EC=2.5.1.1;
CC Evidence={ECO:0000269|PubMed:21237161, ECO:0000269|PubMed:30301210};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22409;
CC Evidence={ECO:0000269|PubMed:21237161, ECO:0000269|PubMed:30301210};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q12051};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};
CC -!- PATHWAY: Isoprenoid biosynthesis; geranyl diphosphate biosynthesis;
CC geranyl diphosphate from dimethylallyl diphosphate and isopentenyl
CC diphosphate: step 1/1. {ECO:0000269|PubMed:21237161}.
CC -!- INDUCTION: Highly up-regulated during the early stages of invasion of
CC the human blood-brain barrier. {ECO:0000269|PubMed:16586367}.
CC -!- DOMAIN: Contains two aspartate-rich motifs, designated as FARM (the
CC first aspartate-rich motif) and SARM (the second aspartate-rich motif).
CC Rv0989c contains arginine in place of the second Asp in its FARM and
CC first Asp in its SARM. The primary role of the FARM and SARM is the
CC chelation of the divalent magnesium ion cofactors that assist substrate
CC binding and catalysis, but it may also play a role in determining
CC product chain length. {ECO:0000305|PubMed:30301210}.
CC -!- DISRUPTION PHENOTYPE: Invasion of the infant human brain microvascular
CC endothelial-cell monolayer is significantly decreased in transposon
CC mutant. {ECO:0000269|PubMed:16586367}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AL123456; CCP43739.1; -; Genomic_DNA.
DR RefSeq; NP_215504.1; NC_000962.3.
DR RefSeq; WP_010886102.1; NZ_NVQJ01000018.1.
DR AlphaFoldDB; O05572; -.
DR SMR; O05572; -.
DR STRING; 83332.Rv0989c; -.
DR PaxDb; O05572; -.
DR PRIDE; O05572; -.
DR DNASU; 885355; -.
DR GeneID; 885355; -.
DR KEGG; mtu:Rv0989c; -.
DR PATRIC; fig|83332.111.peg.1097; -.
DR TubercuList; Rv0989c; -.
DR eggNOG; COG0142; Bacteria.
DR OMA; GKQMRPM; -.
DR PhylomeDB; O05572; -.
DR UniPathway; UPA00259; UER00368.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0004161; F:dimethylallyltranstransferase 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:0033384; P:geranyl 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 Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 1.
PE 1: Evidence at protein level;
KW Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW Reference proteome; Transferase.
FT CHAIN 1..325
FT /note="Dimethylallyltranstransferase"
FT /id="PRO_0000451294"
FT MOTIF 91..95
FT /note="DDXXD motif"
FT /evidence="ECO:0000305|PubMed:30301210"
FT MOTIF 217..221
FT /note="DDXXD motif"
FT /evidence="ECO:0000305|PubMed:30301210"
FT BINDING 54
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 84
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 95
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 95
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="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 92
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000305|PubMed:30301210"
FT SITE 217
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000305|PubMed:30301210"
FT MUTAGEN 92
FT /note="R->D: Leads to the production of longer chain
FT product, specifically (E,E)-farnesyl diphosphate (FPP), in
FT addition to GPP."
FT /evidence="ECO:0000269|PubMed:30301210"
FT MUTAGEN 217
FT /note="R->D: Leads to the production of longer chain
FT product, specifically (E,E)-farnesyl diphosphate (FPP), in
FT addition to GPP."
FT /evidence="ECO:0000269|PubMed:30301210"
SQ SEQUENCE 325 AA; 34757 MW; 95781FA1266BF960 CRC64;
MIPAVSLGDP QFTANVHDGI ARITELINSE LSQADEVMRD TVAHLVDAGG TPFRPLFTVL
AAQLGSDPDG WEVTVAGAAI ELMHLGTLCH DRVVDESDMS RKTPSDNTRW TNNFAILAGD
YRFATASQLA SRLDPEAFAV VAEAFAELIT GQMRATRGPA SHIDTIEHYL RVVHEKTGSL
IAASGQLGAA LSGAAEEQIR RVARLGRMIG AAFEISRDII AISGDSATLS GADLGQAVHT
LPMLYALREQ TPDTSRLREL LAGPIHDDHV AEALTLLRCS PGIGKAKNVV AAYAAQAREE
LPYLPDRQPR RALATLIDHA ISACD
