HEXB_MICLU
ID HEXB_MICLU Reviewed; 325 AA.
AC O66129;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Hexaprenyl-diphosphate synthase large subunit ((2E,6E)-farnesyl-diphosphate specific);
DE Short=HexPS;
DE EC=2.5.1.83;
DE AltName: Full=Hexaprenyl diphosphate synthase;
DE AltName: Full=Hexaprenyl pyrophosphate synthetase;
GN Name=hexs-b;
OS Micrococcus luteus (Micrococcus lysodeikticus).
OC Bacteria; Actinobacteria; Micrococcales; Micrococcaceae; Micrococcus.
OX NCBI_TaxID=1270;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION AS A HEXAPRENYL-DIPHOSPHATE
RP SYNTHASE, CATALYTIC ACTIVITY, AND NOMENCLATURE.
RC STRAIN=B-P 26;
RX PubMed=9515931; DOI=10.1128/jb.180.6.1578-1581.1998;
RA Shimizu N., Koyama T., Ogura K.;
RT "Molecular cloning, expression, and characterization of the genes encoding
RT the two essential protein components of Micrococcus luteus B-P 26
RT hexaprenyl diphosphate synthase.";
RL J. Bacteriol. 180:1578-1581(1998).
RN [2]
RP FUNCTION AS A HEXAPRENYL-DIPHOSPHATE SYNTHASE.
RX PubMed=7174655; DOI=10.1016/s0021-9258(18)33320-9;
RA Fujii H., Koyama T., Ogura K.;
RT "Hexaprenyl pyrophosphate synthetase from Micrococcus luteus B-P 26.
RT Separation of two essential components.";
RL J. Biol. Chem. 257:14610-14612(1982).
RN [3]
RP FUNCTION AS A HEXAPRENYL-DIPHOSPHATE SYNTHASE.
RC STRAIN=B-P 26;
RX PubMed=11514159; DOI=10.1016/s0960-894x(01)00391-2;
RA Nagaki M., Kimura K., Kimura H., Maki Y., Goto E., Nishino T., Koyama T.;
RT "Artificial substrates of medium-chain elongating enzymes, hexaprenyl- and
RT heptaprenyl diphosphate synthases.";
RL Bioorg. Med. Chem. Lett. 11:2157-2159(2001).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS
RP AND MAGNESIUM IONS, REACTION MECHANISM, AND SUBUNIT.
RC STRAIN=B-P 26;
RX PubMed=21068379; DOI=10.1074/jbc.m110.147991;
RA Sasaki D., Fujihashi M., Okuyama N., Kobayashi Y., Noike M., Koyama T.,
RA Miki K.;
RT "Crystal structure of heterodimeric hexaprenyl diphosphate synthase from
RT Micrococcus luteus B-P 26 reveals that the small subunit is directly
RT involved in the product chain length regulation.";
RL J. Biol. Chem. 286:3729-3740(2011).
CC -!- FUNCTION: Catalyzes the condensation of three molecules of isopentenyl
CC diphosphate with farnesyl diphosphate (FPP) to yield (all-E)-hexaprenyl
CC diphosphate (HexPP; C30), the precursor of the prenyl side chain of
CC menaquinone-6. Large subunit Hexs-B catalyzes the condensation reaction
CC and the final product chain length is cooperatively regulated by both
CC the Hexs-A and Hexs-B subunits using the whole size of the hydrophobic
CC cleft as a ruler. {ECO:0000269|PubMed:11514159,
CC ECO:0000269|PubMed:7174655, ECO:0000269|PubMed:9515931}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2E,6E)-farnesyl diphosphate + 3 isopentenyl diphosphate =
CC all-trans-hexaprenyl diphosphate + 3 diphosphate;
CC Xref=Rhea:RHEA:27559, ChEBI:CHEBI:33019, ChEBI:CHEBI:58179,
CC ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.83;
CC Evidence={ECO:0000269|PubMed:9515931};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Dimer of heterodimer or heterotetramer composed of a small
CC (Hexs-a) and large (Hexs-B) subunit. {ECO:0000269|PubMed:21068379}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; AB003188; BAA25268.1; -; Genomic_DNA.
DR PDB; 3AQB; X-ray; 2.40 A; B/D=1-325.
DR PDB; 3AQC; X-ray; 2.61 A; B/D=1-325.
DR PDBsum; 3AQB; -.
DR PDBsum; 3AQC; -.
DR AlphaFoldDB; O66129; -.
DR SMR; O66129; -.
DR KEGG; ag:BAA25268; -.
DR BioCyc; MetaCyc:MON-13829; -.
DR BRENDA; 2.5.1.83; 3348.
DR EvolutionaryTrace; O66129; -.
DR GO; GO:0036423; F:hexaprenyl-diphosphate synthase ((2E,6E)-farnesyl-diphosphate specific) activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IDA:UniProtKB.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IEA:InterPro.
DR GO; GO:0009234; P:menaquinone biosynthetic process; IEA:UniProtKB-KW.
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 3D-structure; Magnesium; Menaquinone biosynthesis; Metal-binding;
KW Transferase.
FT CHAIN 1..325
FT /note="Hexaprenyl-diphosphate synthase large subunit
FT ((2E,6E)-farnesyl-diphosphate specific)"
FT /id="PRO_0000419164"
FT BINDING 45
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 48
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 77
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 84
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21068379,
FT ECO:0007744|PDB:3AQB"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21068379,
FT ECO:0007744|PDB:3AQB"
FT BINDING 88
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT BINDING 88
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:21068379,
FT ECO:0007744|PDB:3AQB"
FT BINDING 88
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:21068379,
FT ECO:0007744|PDB:3AQB"
FT BINDING 93
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT /evidence="ECO:0000250"
FT BINDING 94
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:P14324"
FT BINDING 170
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT BINDING 171
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT /evidence="ECO:0000250"
FT BINDING 208
FT /ligand="all-trans-hexaprenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:58179"
FT /evidence="ECO:0000250"
FT HELIX 6..25
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 47..56
FT /evidence="ECO:0007829|PDB:3AQB"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:3AQC"
FT HELIX 64..88
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 105..122
FT /evidence="ECO:0007829|PDB:3AQB"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 129..151
FT /evidence="ECO:0007829|PDB:3AQB"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 172..184
FT /evidence="ECO:0007829|PDB:3AQB"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 190..217
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 220..223
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 238..249
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 254..260
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 268..281
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 283..302
FT /evidence="ECO:0007829|PDB:3AQB"
FT HELIX 308..320
FT /evidence="ECO:0007829|PDB:3AQB"
FT TURN 321..324
FT /evidence="ECO:0007829|PDB:3AQB"
SQ SEQUENCE 325 AA; 37083 MW; E73A7D6B94DA33F3 CRC64;
MIALSYKAFL NPYIIEVEKR LYECIQSDSE TINKAAHHIL SSGGKRVRPM FVLLSGFLND
TQKDDLIRTA VSLELVHMAS LVHDDYIDNS DMRRGNTSVH IAFDKDTAIR TGHFLLARAL
QNIATINNSK FHQIFSKTIL EVCFGEFDQM ADRFNYPVSF TAYLRRINRK TAILIEASCH
LGALSSQLDE QSTYHIKQFG HCIGMSYQII DDILDYTSDE ATLGKPVGSD IRNGHITYPL
MAAIANLKEQ DDDKLEAVVK HLTSTSDDEV YQYIVSQVKQ YGIEPAELLS RKYGDKAKYH
LSQLQDSNIK DYLEEIHEKM LKRVY
