GGR_SULAC
ID GGR_SULAC Reviewed; 452 AA.
AC Q4JA33;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Digeranylgeranylglycerophospholipid reductase;
DE Short=DGGGPL reductase;
DE EC=1.3.-.- {ECO:0000269|PubMed:18375567, ECO:0000269|PubMed:24954619};
DE AltName: Full=2,3-bis-O-geranylgeranylglyceryl phosphate reductase;
DE AltName: Full=Geranylgeranyl diphosphate reductase;
DE Short=GGPP reductase;
DE AltName: Full=Geranylgeranyl reductase {ECO:0000303|PubMed:18375567};
DE Short=GGR {ECO:0000303|PubMed:18375567};
GN OrderedLocusNames=Saci_0986 {ECO:0000312|EMBL:AAY80347.1};
OS Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC
OS 15157 / NCIMB 11770).
OC Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
OC Sulfolobus.
OX NCBI_TaxID=330779;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770;
RX PubMed=15995215; DOI=10.1128/jb.187.14.4992-4999.2005;
RA Chen L., Bruegger K., Skovgaard M., Redder P., She Q., Torarinsson E.,
RA Greve B., Awayez M., Zibat A., Klenk H.-P., Garrett R.A.;
RT "The genome of Sulfolobus acidocaldarius, a model organism of the
RT Crenarchaeota.";
RL J. Bacteriol. 187:4992-4999(2005).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, FLAVIN-BINDING, COFACTOR, AND PATHWAY.
RX PubMed=18375567; DOI=10.1128/jb.00082-08;
RA Sato S., Murakami M., Yoshimura T., Hemmi H.;
RT "Specific partial reduction of geranylgeranyl diphosphate by an enzyme from
RT the thermoacidophilic archaeon Sulfolobus acidocaldarius yields a reactive
RT prenyl donor, not a dead-end product.";
RL J. Bacteriol. 190:3923-3929(2008).
RN [3] {ECO:0007744|PDB:3ATQ, ECO:0007744|PDB:3ATR}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) IN COMPLEX WITH FADH2, FUNCTION,
RP COFACTOR, DISULFIDE BOND, SUBUNIT, AND MUTAGENESIS OF CYS-47; TYR-215;
RP TRP-217 AND PHE-219.
RX PubMed=21515284; DOI=10.1016/j.jmb.2011.04.002;
RA Sasaki D., Fujihashi M., Iwata Y., Murakami M., Yoshimura T., Hemmi H.,
RA Miki K.;
RT "Structure and mutation analysis of archaeal geranylgeranyl reductase.";
RL J. Mol. Biol. 409:543-557(2011).
RN [4] {ECO:0007744|PDB:4OPC, ECO:0007744|PDB:4OPD, ECO:0007744|PDB:4OPG, ECO:0007744|PDB:4OPI, ECO:0007744|PDB:4OPL, ECO:0007744|PDB:4OPT, ECO:0007744|PDB:4OPU}
RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF WILD-TYPE AND MUTANTS HIS-91;
RP PHE-206; LEU-219; HIS-377 AND PHE-206/HIS-377 IN COMPLEXES WITH FAD;
RP GERANYLGERANYL PYROPHOSPHATE AND PHOSPHATIDYLGLYCEROL, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, DISULFIDE BOND,
RP MUTAGENESIS OF GLY-91; ILE-206; PHE-219 AND LEU-377, AND REACTION
RP MECHANISM.
RX PubMed=24954619; DOI=10.1016/j.str.2014.05.007;
RA Kung Y., McAndrew R.P., Xie X., Liu C.C., Pereira J.H., Adams P.D.,
RA Keasling J.D.;
RT "Constructing tailored isoprenoid products by structure-guided modification
RT of geranylgeranyl reductase.";
RL Structure 22:1028-1036(2014).
CC -!- FUNCTION: Is involved in the reduction of 2,3-
CC digeranylgeranylglycerophospholipids (unsaturated archaeols) into 2,3-
CC diphytanylglycerophospholipids (saturated archaeols) in the
CC biosynthesis of archaeal membrane lipids. Catalyzes the formation of
CC archaetidic acid (2,3-di-O-phytanyl-sn-glyceryl phosphate) from 2,3-di-
CC O-geranylgeranylglyceryl phosphate (DGGGP) via the hydrogenation of
CC each double bond of the isoprenoid chains. Is not active with NADPH or
CC NADH as an electron donor; the physiological reducing agent is unknown.
CC Is also active on the more upstream precursors of membrane lipid
CC biosynthesis, catalyzing the complete reduction of 3-O-
CC geranylgeranylglyceryl phosphate (GGGP) to 3-O-phytanylglyceryl
CC phosphate, and the partial reduction of geranylgeranyl diphosphate
CC (GGPP) to phytyl diphosphate, thus reducing three of four GGPP double
CC bonds and preserving the allylic double bond (at position 2). This
CC reaction product is a reactive prenyl donor, which can be used as a
CC substrate by archaeal prenyltransferases such as GGGP synthases.
CC {ECO:0000269|PubMed:18375567, ECO:0000269|PubMed:21515284,
CC ECO:0000269|PubMed:24954619}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8 A + a 2,3-bis-O-phytanyl-sn-glycerol 1-phospholipid = a 2,3-
CC bis-O-(geranylgeranyl)-sn-glycerol 1-phospholipid + 8 AH2;
CC Xref=Rhea:RHEA:64376, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:138139, ChEBI:CHEBI:138140;
CC Evidence={ECO:0000305|PubMed:18375567, ECO:0000305|PubMed:24954619};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64378;
CC Evidence={ECO:0000305|PubMed:18375567};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2,3-bis-O-(phytanyl)-sn-glycerol 1-phosphate + 8 A = 2,3-bis-
CC O-(geranylgeranyl)-sn-glycerol 1-phosphate + 8 AH2;
CC Xref=Rhea:RHEA:64368, ChEBI:CHEBI:13193, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:58837, ChEBI:CHEBI:73125;
CC Evidence={ECO:0000269|PubMed:18375567};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64370;
CC Evidence={ECO:0000305|PubMed:18375567};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4 A + sn-3-O-phytanylglycerol 1-phosphate = 4 AH2 + sn-3-O-
CC (geranylgeranyl)glycerol 1-phosphate; Xref=Rhea:RHEA:64388,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:17499, ChEBI:CHEBI:57677,
CC ChEBI:CHEBI:152569; Evidence={ECO:0000269|PubMed:18375567};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64390;
CC Evidence={ECO:0000305|PubMed:18375567};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 A + phytyl diphosphate = (2E,6E,10E)-geranylgeranyl
CC diphosphate + 3 AH2; Xref=Rhea:RHEA:64380, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:58756, ChEBI:CHEBI:75434;
CC Evidence={ECO:0000269|PubMed:18375567, ECO:0000269|PubMed:24954619};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:64382;
CC Evidence={ECO:0000305|PubMed:18375567};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:21515284, ECO:0000269|PubMed:24954619,
CC ECO:0000305|PubMed:18375567};
CC Note=Binds 1 FAD per subunit. {ECO:0000269|PubMed:21515284,
CC ECO:0000269|PubMed:24954619};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Note=kcat is 0.40 min(-1) for the reduction of GGPP to the hexahydro-
CC product H(6)GGPP. {ECO:0000269|PubMed:24954619};
CC pH dependence:
CC Optimum pH is 5.5 for the reduction of GGPP to the hexahydro-product
CC H(6)GGPP. {ECO:0000269|PubMed:24954619};
CC Temperature dependence:
CC Optimum temperature is 55 degrees Celsius for the reduction of GGPP
CC to the hexahydro-product H(6)GGPP. {ECO:0000269|PubMed:24954619};
CC -!- PATHWAY: Membrane lipid metabolism; glycerophospholipid metabolism.
CC {ECO:0000305|PubMed:18375567}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21515284}.
CC -!- SIMILARITY: Belongs to the geranylgeranyl reductase family.
CC {ECO:0000305}.
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DR EMBL; CP000077; AAY80347.1; -; Genomic_DNA.
DR RefSeq; WP_011277849.1; NC_007181.1.
DR PDB; 3ATQ; X-ray; 1.85 A; A=1-452.
DR PDB; 3ATR; X-ray; 1.80 A; A=1-452.
DR PDB; 4OPC; X-ray; 1.40 A; A=1-452.
DR PDB; 4OPD; X-ray; 1.81 A; A/B=1-452.
DR PDB; 4OPG; X-ray; 2.07 A; A=1-452.
DR PDB; 4OPI; X-ray; 2.24 A; A=1-452.
DR PDB; 4OPL; X-ray; 2.51 A; A=1-452.
DR PDB; 4OPT; X-ray; 2.60 A; A=1-452.
DR PDB; 4OPU; X-ray; 2.70 A; A=1-452.
DR PDBsum; 3ATQ; -.
DR PDBsum; 3ATR; -.
DR PDBsum; 4OPC; -.
DR PDBsum; 4OPD; -.
DR PDBsum; 4OPG; -.
DR PDBsum; 4OPI; -.
DR PDBsum; 4OPL; -.
DR PDBsum; 4OPT; -.
DR PDBsum; 4OPU; -.
DR AlphaFoldDB; Q4JA33; -.
DR SMR; Q4JA33; -.
DR STRING; 330779.Saci_0986; -.
DR EnsemblBacteria; AAY80347; AAY80347; Saci_0986.
DR GeneID; 3473654; -.
DR KEGG; sai:Saci_0986; -.
DR PATRIC; fig|330779.12.peg.946; -.
DR eggNOG; arCOG00570; Archaea.
DR HOGENOM; CLU_024648_0_0_2; -.
DR OMA; WYFPRTE; -.
DR BRENDA; 1.3.7.11; 6160.
DR UniPathway; UPA00940; -.
DR EvolutionaryTrace; Q4JA33; -.
DR Proteomes; UP000001018; Chromosome.
DR GO; GO:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; IEA:InterPro.
DR GO; GO:0006650; P:glycerophospholipid metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR006076; FAD-dep_OxRdtase.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR InterPro; IPR011777; Geranylgeranyl_Rdtase_fam.
DR Pfam; PF01266; DAO; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
DR TIGRFAMs; TIGR02032; GG-red-SF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; FAD; Flavoprotein; Lipid biosynthesis;
KW Lipid metabolism; Oxidoreductase; Phospholipid biosynthesis;
KW Phospholipid metabolism; Reference proteome.
FT CHAIN 1..452
FT /note="Digeranylgeranylglycerophospholipid reductase"
FT /id="PRO_0000450802"
FT BINDING 15..16
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 35..36
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 45..50
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 55
FT /ligand="a 2,3-bis-O-phytanyl-sn-glycerol 1-phospholipid"
FT /ligand_id="ChEBI:CHEBI:138139"
FT /evidence="ECO:0000305|PubMed:24954619,
FT ECO:0007744|PDB:4OPC"
FT BINDING 122
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 288
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 297
FT /ligand="a 2,3-bis-O-phytanyl-sn-glycerol 1-phospholipid"
FT /ligand_id="ChEBI:CHEBI:138139"
FT /evidence="ECO:0000305|PubMed:24954619,
FT ECO:0007744|PDB:4OPC"
FT BINDING 300..301
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:4OPC"
FT BINDING 340
FT /ligand="a 2,3-bis-O-phytanyl-sn-glycerol 1-phospholipid"
FT /ligand_id="ChEBI:CHEBI:138139"
FT /evidence="ECO:0000305|PubMed:24954619,
FT ECO:0007744|PDB:4OPC"
FT DISULFID 310..335
FT /evidence="ECO:0000269|PubMed:21515284,
FT ECO:0000269|PubMed:24954619, ECO:0007744|PDB:3ATQ,
FT ECO:0007744|PDB:3ATR, ECO:0007744|PDB:4OPC"
FT MUTAGEN 47
FT /note="C->A,M: Almost loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:21515284"
FT MUTAGEN 47
FT /note="C->S: Seems to be able to reduce only one double
FT bond of GGGP."
FT /evidence="ECO:0000269|PubMed:21515284"
FT MUTAGEN 91
FT /note="G->H: Halts the reduction of GGPP at H(2)GGPP."
FT /evidence="ECO:0000269|PubMed:24954619"
FT MUTAGEN 206
FT /note="I->F: Increases reduction rate of GGPP to H(6)GGPP."
FT /evidence="ECO:0000269|PubMed:24954619"
FT MUTAGEN 215
FT /note="Y->F,L: Moderate decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:21515284"
FT MUTAGEN 217
FT /note="W->L: Large decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:21515284"
FT MUTAGEN 219
FT /note="F->L: Halts the reduction of GGPP at H(4)GGPP."
FT /evidence="ECO:0000269|PubMed:24954619"
FT MUTAGEN 219
FT /note="F->L: Slight decrease in catalytic activity."
FT /evidence="ECO:0000269|PubMed:21515284"
FT MUTAGEN 377
FT /note="L->H: Increases reduction rate of GGPP to H(6)GGPP."
FT /evidence="ECO:0000269|PubMed:24954619"
FT STRAND 2..5
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 25..28
FT /evidence="ECO:0007829|PDB:3ATR"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 53..59
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 69..79
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 86..96
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 98..111
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 115..128
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 131..139
FT /evidence="ECO:0007829|PDB:4OPC"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 164..166
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 182..194
FT /evidence="ECO:0007829|PDB:4OPC"
FT TURN 197..200
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 201..205
FT /evidence="ECO:0007829|PDB:4OPC"
FT TURN 208..210
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 214..236
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 241..252
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 256..270
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:4OPC"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 287..290
FT /evidence="ECO:0007829|PDB:4OPC"
FT TURN 295..297
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 301..321
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 331..339
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 341..356
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 359..367
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 373..382
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 387..396
FT /evidence="ECO:0007829|PDB:4OPC"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 405..408
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 409..424
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 430..432
FT /evidence="ECO:0007829|PDB:4OPC"
FT HELIX 433..451
FT /evidence="ECO:0007829|PDB:4OPC"
SQ SEQUENCE 452 AA; 50623 MW; 1C94FC2B23BA3CDF CRC64;
MKELKYDVLI IGGGFAGSSA AYQLSRRGLK ILLVDSKPWN RIGDKPCGDA VSKAHFDKLG
MPYPKGEELE NKINGIKLYS PDMQTVWTVN GEGFELNAPL YNQRVLKEAQ DRGVEIWDLT
TAMKPIFEDG YVKGAVLFNR RTNEELTVYS KVVVEATGYS RSFRSKLPPE LPITEDLDDK
DADVAYREVL LTKEDIEDHD YLRIFIDQET SPGGYWWYFP KGKNKVNVGL GIQGGMGYPS
IHEYYKKYLD KYAPDVDKSK LLVKGGALVP TRRPLYTMAW NGIIVIGDSG FTVNPVHGGG
KGSAMISGYC AAKAILSAFE TGDFSASGLW DMNICYVNEY GAKQASLDIF RRFLQKLSND
DINYGMKKKI IKEEDLLEAS EKGDLHLSVA DKAMRVISGL GRPSLLFKLK AVAESMKKIK
ELYLNYPRSP SSLGSWRREV DNVLTEFNKS LS
