PLE4_RHOPP
ID PLE4_RHOPP Reviewed; 350 AA.
AC A0A6S6QJ62;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 1.
DT 03-AUG-2022, entry version 6.
DE RecName: Full=Geranylgeranyl pyrophosphate synthase {ECO:0000303|PubMed:28924980};
DE Short=GGPP synthase {ECO:0000250|UniProtKB:Q12051};
DE Short=GGPPSase {ECO:0000250|UniProtKB:Q12051};
DE Short=GGS {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.- {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=(2E,6E)-farnesyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Dimethylallyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.1 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Farnesyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Farnesyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.29 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Geranylgeranyl diphosphate synthase {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Geranyltranstransferase {ECO:0000250|UniProtKB:Q12051};
DE EC=2.5.1.10 {ECO:0000250|UniProtKB:Q12051};
DE AltName: Full=Pleuromutilin biosynthetic cluster protein synthesis protein 4 {ECO:0000303|PubMed:28924980};
GN Name=ple4 {ECO:0000303|PubMed:28924980};
OS Rhodocybe pseudopiperita (Clitopilus pseudopiperitus).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Entolomataceae; Rhodocybe.
OX NCBI_TaxID=693819;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=ATCC 20527;
RX PubMed=28924980; DOI=10.1002/cbic.201700434;
RA Yamane M., Minami A., Liu C., Ozaki T., Takeuchi I., Tsukagoshi T.,
RA Tokiwano T., Gomi K., Oikawa H.;
RT "Biosynthetic machinery of diterpene pleuromutilin isolated from
RT basidiomycete fungi.";
RL ChemBioChem 18:2317-2322(2017).
CC -!- FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene
CC cluster that mediates the biosynthesis of pleuromutilin, a tricyclic
CC diterpene showing antibacterial properties (PubMed:28924980). The
CC geranylgeranyl diphosphate (GGPP) synthase ple4 catalyzes the first
CC step in pleuromutilin biosynthesis (PubMed:28924980). GGPP is then
CC substrate of the premutilin synthase (PS) ple3 to yield premutilin
CC (PubMed:28924980). Premutilin synthase is a bifunctional enzyme
CC composed of the fusion of a class II diterpene cyclase (DTC) and a
CC class I diterpene synthase (DTS), with the corresponding domains and
CC active sites containing characteristic aspartate-rich motifs (By
CC similarity). GGPP is first converted to mutildienyl-diphosphate (MPP)
CC at the class II DTC site (By similarity). MPP is subsequently further
CC cyclized at the class I DTS site, followed by a 1,5-hydride shift and
CC addition of water prior to terminating deprotonation, to yield
CC premutilin (By similarity). The cytochrome P450 monooxygenases ple5 and
CC ple6 hydroxylate premutilin at C-11 and C-3, respectively, producing
CC 11-hydroxypremutilin and 3-hydroxypremutilin (PubMed:28924980). The
CC combination of the actions of both ple5 and ple6 leads to the
CC production of 3,11-dihydroxypremutilin (PubMed:28924980). The short
CC chain dehydrogenase ple7 further converts 3,11-dihydroxypremutilin into
CC mutilin (PubMed:28924980). The acetyltransferase ple2 then acetylates
CC mutilin to produce 14-O-acetylmutilin (PubMed:28924980). Finally, the
CC cytochrome P450 monooxygenase ple1 catalyzes hydroxylation on the alpha
CC position of the acetyl side chain of 14-O-acetylmutilin to yield
CC pleuromutilin (PubMed:28924980). {ECO:0000250|UniProtKB:A0A2L0VXR0,
CC ECO:0000269|PubMed:28924980}.
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:0000250|UniProtKB:Q12051};
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:0000250|UniProtKB:Q12051};
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:0000250|UniProtKB:Q12051};
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: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:28924980}.
CC -!- SIMILARITY: Belongs to the FPP/GGPP synthase family. {ECO:0000305}.
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DR EMBL; LC314149; BCI98772.1; -; Genomic_DNA.
DR SMR; A0A6S6QJ62; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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 Antibiotic biosynthesis; Isoprene biosynthesis; Magnesium; Metal-binding;
KW Transferase.
FT CHAIN 1..350
FT /note="Geranylgeranyl pyrophosphate synthase"
FT /id="PRO_0000453729"
FT BINDING 66
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 69
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 98
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 105
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 109
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 109
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 114
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 115
FT /ligand="isopentenyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:128769"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 200
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 201
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 236
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 243
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 263
FT /ligand="dimethylallyl diphosphate"
FT /ligand_id="ChEBI:CHEBI:57623"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT SITE 137
FT /note="Important for determining product chain length"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 350 AA; 39174 MW; 005A0C23CA929081 CRC64;
MRIPNIFLSY LRQVAVDGTL SSCSGVKSRK PVIAFGFDDS QDSLVDENDE KILEPFGYYR
HLLKGKSART VLMHCFNAFL GLPEDWVLGV TKAIEDLHNA SLLIDDIEDE SALRRGSPAA
HMKYGIALTM NAGNLVYFTV LQDIYDLGMR TGGTQVANAM AHIYTEEMIE LHRGQGIEIW
WRDQRSPPSV DQYIHMLEQK TGGLLRLGVR LLQCHPGGNN RADLSAIALR IGVYYQLRDD
YINLMSTSYH DERGFAEDIT EGKYTFPMLH SLKRSPDSGL REILDLKPAD IALKKKAIAI
MQETGSLIAT RNLLGAVKND LSGLVAEQRG DDYAMSAGLE RFLEKLYIAE
