ISPD_ECOLI
ID ISPD_ECOLI Reviewed; 236 AA.
AC Q46893; Q2MA82;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase;
DE EC=2.7.7.60;
DE AltName: Full=4-diphosphocytidyl-2C-methyl-D-erythritol synthase;
DE AltName: Full=CDP-ME synthase;
DE AltName: Full=MEP cytidylyltransferase;
DE Short=MCT;
GN Name=ispD; Synonyms=ygbP; OrderedLocusNames=b2747, JW2717;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, AND
RP CHARACTERIZATION.
RC STRAIN=K12 / DH5-alpha;
RX PubMed=10518523; DOI=10.1073/pnas.96.21.11758;
RA Rohdich F., Wungsintaweekul J., Fellermeier M., Sagner S., Herz S., Kis K.,
RA Eisenreich W., Bacher A., Zenk M.H.;
RT "Cytidine 5'-triphosphate-dependent biosynthesis of isoprenoids: YgbP
RT protein of Escherichia coli catalyzes the formation of 4-diphosphocytidyl-
RT 2-C-methylerythritol.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:11758-11763(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Kuzuyama T., Takagi M., Kaneda K., Dairi T., Seto H.;
RT "Formation of 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol from 2-C-
RT methyl-D-erythritol 4-phosphate by 2-C-methyl-D-erythritol 4-phosphate
RT cytidylyltransferase, a new enzyme in the nonmevalonate pathway.";
RL Tetrahedron Lett. 41:703-706(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP MUTAGENESIS OF THR-140 AND GLU-191.
RX PubMed=12859972; DOI=10.1016/s0006-291x(03)01211-7;
RA Sauret-Gueeto S., Ramos-Valdivia A., Ibanez E., Boronat A.,
RA Rodriguez-Concepcion M.;
RT "Identification of lethal mutations in Escherichia coli genes encoding
RT enzymes of the methylerythritol phosphate pathway.";
RL Biochem. Biophys. Res. Commun. 307:408-415(2003).
RN [6]
RP CRYSTALLIZATION.
RX PubMed=11468415; DOI=10.1107/s0907444901010137;
RA Kemp L.E., Bond C.S., Hunter W.N.;
RT "Crystallization and preliminary X-ray diffraction studies of recombinant
RT Escherichia coli 4-diphosphocytidyl-2-C-methyl-D-erythritol synthetase.";
RL Acta Crystallogr. D 57:1189-1191(2001).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) IN COMPLEX WITH CTP-MG(2+) AND IN
RP COMPLEX WITH CDP-ME-MG(2+), AND MUTAGENESIS OF LYS-27 AND LYS-213.
RC STRAIN=K12;
RX PubMed=11427897; DOI=10.1038/89691;
RA Richard S.B., Bowman M.E., Kwiatkowski W., Kang I., Chow C., Lillo A.M.,
RA Cane D.E., Noel J.P.;
RT "Structure of 4-diphosphocytidyl-2-C-methylerythritol synthetase involved
RT in mevalonate-independent isoprenoid biosynthesis.";
RL Nat. Struct. Biol. 8:641-648(2001).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=12595740; DOI=10.1107/s090744490202365x;
RA Kemp L.E., Bond C.S., Hunter W.N.;
RT "Structure of a tetragonal crystal form of Escherichia coli 2-C-methyl-D-
RT erythritol 4-phosphate cytidylyltransferase.";
RL Acta Crystallogr. D 59:607-610(2003).
CC -!- FUNCTION: Catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-
CC erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP).
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.3.;
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC phosphate: step 2/6.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11427897}.
CC -!- MISCELLANEOUS: There are no coordination bonds that occur between IspD
CC and magnesium in any of the complexes examined to date.
CC -!- SIMILARITY: Belongs to the IspD/TarI cytidylyltransferase family. IspD
CC subfamily. {ECO:0000305}.
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DR EMBL; AF230736; AAF43207.1; -; Genomic_DNA.
DR EMBL; AB037143; BAA90761.1; -; Genomic_DNA.
DR EMBL; U29579; AAA69257.1; -; Genomic_DNA.
DR EMBL; U00096; AAC75789.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76824.1; -; Genomic_DNA.
DR PIR; G65055; G65055.
DR RefSeq; NP_417227.1; NC_000913.3.
DR RefSeq; WP_000246138.1; NZ_STEB01000027.1.
DR PDB; 1H3M; X-ray; 2.40 A; A/B=2-236.
DR PDB; 1I52; X-ray; 1.50 A; A=1-236.
DR PDB; 1INI; X-ray; 1.82 A; A=1-236.
DR PDB; 1INJ; X-ray; 1.55 A; A=1-236.
DR PDB; 1VGT; X-ray; 1.80 A; A/B=2-236.
DR PDB; 1VGU; X-ray; 2.80 A; A/B=2-236.
DR PDB; 3N9W; X-ray; 1.90 A; A/B=2-236.
DR PDBsum; 1H3M; -.
DR PDBsum; 1I52; -.
DR PDBsum; 1INI; -.
DR PDBsum; 1INJ; -.
DR PDBsum; 1VGT; -.
DR PDBsum; 1VGU; -.
DR PDBsum; 3N9W; -.
DR AlphaFoldDB; Q46893; -.
DR SMR; Q46893; -.
DR BioGRID; 4262280; 173.
DR IntAct; Q46893; 2.
DR STRING; 511145.b2747; -.
DR DrugBank; DB03687; 4-(Cytidine 5'-diphospho)-2-C-methyl-D-erythritol.
DR DrugBank; DB03854; Cadaverine.
DR DrugBank; DB02431; Cytidine-5'-Triphosphate.
DR jPOST; Q46893; -.
DR PaxDb; Q46893; -.
DR PRIDE; Q46893; -.
DR EnsemblBacteria; AAC75789; AAC75789; b2747.
DR EnsemblBacteria; BAE76824; BAE76824; BAE76824.
DR GeneID; 948269; -.
DR KEGG; ecj:JW2717; -.
DR KEGG; eco:b2747; -.
DR PATRIC; fig|1411691.4.peg.3993; -.
DR EchoBASE; EB2913; -.
DR eggNOG; COG1211; Bacteria.
DR HOGENOM; CLU_061281_3_1_6; -.
DR InParanoid; Q46893; -.
DR OMA; ERQHSVY; -.
DR PhylomeDB; Q46893; -.
DR BioCyc; EcoCyc:G7423-MON; -.
DR BioCyc; MetaCyc:G7423-MON; -.
DR BRENDA; 2.7.7.60; 2026.
DR SABIO-RK; Q46893; -.
DR UniPathway; UPA00056; UER00093.
DR EvolutionaryTrace; Q46893; -.
DR PRO; PR:Q46893; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0050518; F:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity; IDA:EcoCyc.
DR GO; GO:0042802; F:identical protein binding; IDA:EcoCyc.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
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 Gene3D; 3.90.550.10; -; 1.
DR HAMAP; MF_00108; IspD; 1.
DR InterPro; IPR001228; IspD.
DR InterPro; IPR034683; IspD/TarI.
DR InterPro; IPR018294; ISPD_synthase_CS.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF01128; IspD; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR TIGRFAMs; TIGR00453; ispD; 1.
DR PROSITE; PS01295; ISPD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cobalt; Direct protein sequencing; Isoprene biosynthesis;
KW Magnesium; Manganese; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..236
FT /note="2-C-methyl-D-erythritol 4-phosphate
FT cytidylyltransferase"
FT /id="PRO_0000075572"
FT SITE 20
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000269|PubMed:11427897"
FT SITE 27
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000269|PubMed:11427897"
FT SITE 157
FT /note="Positions MEP for the nucleophilic attack"
FT /evidence="ECO:0000269|PubMed:11427897"
FT SITE 213
FT /note="Positions MEP for the nucleophilic attack"
FT /evidence="ECO:0000269|PubMed:11427897"
FT MUTAGEN 27
FT /note="K->A,S: Strong decrease in activity."
FT /evidence="ECO:0000269|PubMed:11427897"
FT MUTAGEN 140
FT /note="T->I: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12859972"
FT MUTAGEN 191
FT /note="E->K: Loss of activity."
FT /evidence="ECO:0000269|PubMed:12859972"
FT MUTAGEN 213
FT /note="K->S: Decrease in activity."
FT /evidence="ECO:0000269|PubMed:11427897"
FT STRAND 8..14
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:1INI"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 37..46
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 51..58
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 69..72
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 85..94
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 114..121
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 131..136
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 141..144
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 148..155
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 161..170
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 171..183
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 191..197
FT /evidence="ECO:0007829|PDB:1I52"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 219..227
FT /evidence="ECO:0007829|PDB:1I52"
FT HELIX 229..233
FT /evidence="ECO:0007829|PDB:3N9W"
SQ SEQUENCE 236 AA; 25737 MW; 6AD26690AC2CF201 CRC64;
MATTHLDVCA VVPAAGFGRR MQTECPKQYL SIGNQTILEH SVHALLAHPR VKRVVIAISP
GDSRFAQLPL ANHPQITVVD GGDERADSVL AGLKAAGDAQ WVLVHDAARP CLHQDDLARL
LALSETSRTG GILAAPVRDT MKRAEPGKNA IAHTVDRNGL WHALTPQFFP RELLHDCLTR
ALNEGATITD EASALEYCGF HPQLVEGRAD NIKVTRPEDL ALAEFYLTRT IHQENT
