ID ISPDF_HELPH Reviewed; 406 AA. AC Q1CU78; DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2006, sequence version 1. DT 04-NOV-2026, entry version 105. 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=HPAG1_0427; OS Helicobacter pylori (strain HPAG1). OC Bacteria; Pseudomonadati; Campylobacterota; Epsilonproteobacteria; OC Campylobacterales; Helicobacteraceae; Helicobacter. OX NCBI_TaxID=357544; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=HPAG1; RX PubMed=16788065; DOI=10.1073/pnas.0603784103; RA Oh J.D., Kling-Baeckhed H., Giannakis M., Xu J., Fulton R.S., Fulton L.A., RA Cordum H.S., Wang C., Elliott G., Edwards J., Mardis E.R., Engstrand L.G., RA Gordon J.I.; RT "The complete genome sequence of a chronic atrophic gastritis Helicobacter RT pylori strain: evolution during disease progression."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9999-10004(2006). 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP000241; ABF84494.1; -; Genomic_DNA. DR RefSeq; WP_000052892.1; NC_008086.1. DR AlphaFoldDB; Q1CU78; -. DR SMR; Q1CU78; -. DR KEGG; hpa:HPAG1_0427; -. DR HOGENOM; CLU_042800_2_6_7; -. DR OMA; AACIVPY; -. DR UniPathway; UPA00056; UER00093. DR UniPathway; UPA00056; UER00095. 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:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol phosphate pathway; IEA:UniProtKB-UniRule. DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:InterPro. DR CDD; cd02516; CDP-ME_synthetase; 1. DR CDD; cd00554; MECDP_synthase; 1. DR FunFam; 3.30.1330.50:FF:000005; Bifunctional enzyme IspD/IspF; 1. DR FunFam; 3.90.550.10:FF:000259; Bifunctional enzyme IspD/IspF; 1. DR Gene3D; 3.30.1330.50; 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; 1. DR Gene3D; 3.90.550.10; Spore Coat Polysaccharide Biosynthesis Protein SpsA, Chain A; 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 NCBIfam; NF006899; PRK09382.1; 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..406 FT /note="Bifunctional enzyme IspD/IspF" FT /id="PRO_0000296747" FT REGION 1..247 FT /note="2-C-methyl-D-erythritol 4-phosphate FT cytidylyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT REGION 248..406 FT /note="2-C-methyl-D-erythritol 2,4-cyclodiphosphate FT synthase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT BINDING 254..256 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 254 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT BINDING 256 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT BINDING 280..281 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 288 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT BINDING 302..304 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 307..311 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 378..381 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 385 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 388 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 48 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT SITE 55 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT SITE 175 FT /note="Positions MEP for the nucleophilic attack" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT SITE 227 FT /note="Positions MEP for the nucleophilic attack" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT SITE 280 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" FT SITE 379 FT /note="Transition state stabilizer" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01520" SQ SEQUENCE 406 AA; 45590 MW; F798BABA3C78313E CRC64; MSLIRVNGEA FKFSLESLEE DPFETKETLE ILVKQTSVVL LAAGESRRFS QTIKKQWLRS NHTPLWLSVY ESFKEALDFK EIVLVVSELD YIYIQRHYPE IKLIKGGASR QESVRNALKI IDSAYTLTSD VARGLANMET LKSLFLTLQQ TSHYCIAPYL PCYDTAIYYN EALDREAIKL IQTPQLSHTK TLQSALNQGD FKDESSAILQ AFPNSVSYIE GSKDLHKLTT SDDLKHFAFF FNPAKDTFIG MGFDTHAFIK DKPMVLGGVV LDCEFGLKAH SDGDALLHAV IDAVLGAIKG GDIGEWFPDN DPKYKNASSK ELLKIVLDFS QSIGFELFEM GATIFSEIPK ITPYKPAILE NLSQLLGLEK SQISLKATTM EKMGFIGKQE GLLVQAHVSM RYKQKL //