ID   ISPDF_BRUME             Reviewed;         390 AA.
AC   Q8YHD8;
DT   06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   27-MAR-2024, entry version 120.
DE   RecName: Full=Bifunctional enzyme IspD/IspF {ECO:0000255|HAMAP-Rule:MF_01520};
DE   Includes:
DE     RecName: Full=2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase {ECO:0000255|HAMAP-Rule:MF_01520};
DE              EC=2.7.7.60 {ECO:0000255|HAMAP-Rule:MF_01520};
DE     AltName: Full=4-diphosphocytidyl-2C-methyl-D-erythritol synthase {ECO:0000255|HAMAP-Rule:MF_01520};
DE     AltName: Full=MEP cytidylyltransferase {ECO:0000255|HAMAP-Rule:MF_01520};
DE              Short=MCT {ECO:0000255|HAMAP-Rule:MF_01520};
DE   Includes:
DE     RecName: Full=2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase {ECO:0000255|HAMAP-Rule:MF_01520};
DE              Short=MECDP-synthase {ECO:0000255|HAMAP-Rule:MF_01520};
DE              Short=MECPP-synthase {ECO:0000255|HAMAP-Rule:MF_01520};
DE              Short=MECPS {ECO:0000255|HAMAP-Rule:MF_01520};
DE              EC=4.6.1.12 {ECO:0000255|HAMAP-Rule:MF_01520};
GN   Name=ispDF {ECO:0000255|HAMAP-Rule:MF_01520};
GN   OrderedLocusNames=BMEI0863;
OS   Brucella melitensis biotype 1 (strain 16M / ATCC 23456 / NCTC 10094).
OC   Bacteria; Pseudomonadota; Alphaproteobacteria; Hyphomicrobiales;
OC   Brucellaceae; Brucella/Ochrobactrum group; Brucella.
OX   NCBI_TaxID=224914;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=16M / ATCC 23456 / NCTC 10094;
RX   PubMed=11756688; DOI=10.1073/pnas.221575398;
RA   DelVecchio V.G., Kapatral V., Redkar R.J., Patra G., Mujer C., Los T.,
RA   Ivanova N., Anderson I., Bhattacharyya A., Lykidis A., Reznik G.,
RA   Jablonski L., Larsen N., D'Souza M., Bernal A., Mazur M., Goltsman E.,
RA   Selkov E., Elzer P.H., Hagius S., O'Callaghan D., Letesson J.-J.,
RA   Haselkorn R., Kyrpides N.C., Overbeek R.;
RT   "The genome sequence of the facultative intracellular pathogen Brucella
RT   melitensis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:443-448(2002).
CC   -!- FUNCTION: Bifunctional enzyme that catalyzes the formation of 4-
CC       diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-
CC       erythritol 4-phosphate (MEP) (IspD), and catalyzes the conversion of 4-
CC       diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-
CC       methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding
CC       release of cytidine 5-monophosphate (CMP) (IspF). {ECO:0000255|HAMAP-
CC       Rule:MF_01520}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2-C-methyl-D-erythritol 4-phosphate + CTP + H(+) = 4-CDP-2-C-
CC         methyl-D-erythritol + diphosphate; Xref=Rhea:RHEA:13429,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563,
CC         ChEBI:CHEBI:57823, ChEBI:CHEBI:58262; EC=2.7.7.60;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01520};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4-CDP-2-C-methyl-D-erythritol 2-phosphate = 2-C-methyl-D-
CC         erythritol 2,4-cyclic diphosphate + CMP; Xref=Rhea:RHEA:23864,
CC         ChEBI:CHEBI:57919, ChEBI:CHEBI:58483, ChEBI:CHEBI:60377; EC=4.6.1.12;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01520};
CC   -!- COFACTOR:
CC       Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_01520};
CC   -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC       via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC       phosphate: step 2/6. {ECO:0000255|HAMAP-Rule:MF_01520}.
CC   -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC       via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC       phosphate: step 4/6. {ECO:0000255|HAMAP-Rule:MF_01520}.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the IspD/TarI
CC       cytidylyltransferase family. IspD subfamily. {ECO:0000255|HAMAP-
CC       Rule:MF_01520}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the IspF family.
CC       {ECO:0000255|HAMAP-Rule:MF_01520}.
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DR   EMBL; AE008917; AAL52044.1; -; Genomic_DNA.
DR   PIR; AI3359; AI3359.
DR   AlphaFoldDB; Q8YHD8; -.
DR   SMR; Q8YHD8; -.
DR   KEGG; bme:BMEI0863; -.
DR   eggNOG; COG0245; Bacteria.
DR   eggNOG; COG1211; Bacteria.
DR   UniPathway; UPA00056; UER00093.
DR   UniPathway; UPA00056; UER00095.
DR   Proteomes; UP000000419; Chromosome I.
DR   GO; GO:0008685; F:2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0050518; F:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IEA:UniProtKB-UniPathway.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniRule.
DR   CDD; cd02516; CDP-ME_synthetase; 1.
DR   CDD; cd00554; MECDP_synthase; 1.
DR   Gene3D; 3.30.1330.50; 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; 1.
DR   HAMAP; MF_01520; IspDF; 1.
DR   HAMAP; MF_00107; IspF; 1.
DR   InterPro; IPR001228; IspD.
DR   InterPro; IPR026596; IspD/F.
DR   InterPro; IPR034683; IspD/TarI.
DR   InterPro; IPR018294; ISPD_synthase_CS.
DR   InterPro; IPR003526; MECDP_synthase.
DR   InterPro; IPR020555; MECDP_synthase_CS.
DR   InterPro; IPR036571; MECDP_synthase_sf.
DR   InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR   NCBIfam; TIGR00453; ispD; 1.
DR   NCBIfam; TIGR00151; ispF; 1.
DR   PANTHER; PTHR43181; 2-C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE, CHLOROPLASTIC; 1.
DR   PANTHER; PTHR43181:SF1; 2-C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE, CHLOROPLASTIC; 1.
DR   Pfam; PF01128; IspD; 1.
DR   Pfam; PF02542; YgbB; 1.
DR   SUPFAM; SSF69765; IpsF-like; 1.
DR   SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1.
DR   PROSITE; PS01295; ISPD; 1.
DR   PROSITE; PS01350; ISPF; 1.
PE   3: Inferred from homology;
KW   Isoprene biosynthesis; Lyase; Metal-binding; Multifunctional enzyme;
KW   Nucleotidyltransferase; Transferase.
FT   CHAIN           1..390
FT                   /note="Bifunctional enzyme IspD/IspF"
FT                   /id="PRO_0000075660"
FT   REGION          1..229
FT                   /note="2-C-methyl-D-erythritol 4-phosphate
FT                   cytidylyltransferase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   REGION          230..390
FT                   /note="2-C-methyl-D-erythritol 2,4-cyclodiphosphate
FT                   synthase"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         236..238
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         236
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         238
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         262..263
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         270
FT                   /ligand="a divalent metal cation"
FT                   /ligand_id="ChEBI:CHEBI:60240"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         284..286
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         360..363
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         367
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   BINDING         370
FT                   /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT                   /ligand_id="ChEBI:CHEBI:57919"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            8
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            17
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            148
FT                   /note="Positions MEP for the nucleophilic attack"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            205
FT                   /note="Positions MEP for the nucleophilic attack"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            262
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
FT   SITE            361
FT                   /note="Transition state stabilizer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_01520"
SQ   SEQUENCE   390 AA;  41840 MW;  05AB0A2FBA03DEDB CRC64;
     MAAGRGERAG QSAEGPKQYR LIGAEAVLAR TLRAFTDCPL IGTIAVVIHP DDHALYRRAV
     PEKHENVILV TGGPTRQEST RLGLLALKDE APQYVLIHDG VRPFIGQDLL ERIIANLTPD
     NGVLPALAVS DTLKRAAADG MVETTISRTG LFAAQTPQAF PYAPILDAHE KAFAINRTDF
     TDDAAIAEWQ EIAVRIIEGS ADNTKLTWAK DIEMADKRLR QDHAVFPDIR TGNGYDVHSF
     EPGDHVTLCG VKIPHEAKLN GHSDADVALH ALTDALLATR GAGDIGTHFP PSDPQWKGAA
     SRIFIEHAAK IVREAGGRIA NVDVTLISEA PKIGPHRAAM TQALCDMLGI AADRVSIKAT
     TNEKLGFVGR REGIAAIATA TVIYPGEVPE
//