ISPF_BURPS
ID ISPF_BURPS Reviewed; 162 AA.
AC Q63T71;
DT 15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase {ECO:0000255|HAMAP-Rule:MF_00107};
DE Short=MECDP-synthase {ECO:0000255|HAMAP-Rule:MF_00107};
DE Short=MECPP-synthase {ECO:0000255|HAMAP-Rule:MF_00107};
DE Short=MECPS {ECO:0000255|HAMAP-Rule:MF_00107};
DE EC=4.6.1.12 {ECO:0000255|HAMAP-Rule:MF_00107};
GN Name=ispF {ECO:0000255|HAMAP-Rule:MF_00107}; Synonyms=mecS;
GN OrderedLocusNames=BPSL2098;
OS Burkholderia pseudomallei (strain K96243).
OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC Burkholderiaceae; Burkholderia; pseudomallei group.
OX NCBI_TaxID=272560;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K96243;
RX PubMed=15377794; DOI=10.1073/pnas.0403302101;
RA Holden M.T.G., Titball R.W., Peacock S.J., Cerdeno-Tarraga A.-M.,
RA Atkins T., Crossman L.C., Pitt T., Churcher C., Mungall K.L., Bentley S.D.,
RA Sebaihia M., Thomson N.R., Bason N., Beacham I.R., Brooks K., Brown K.A.,
RA Brown N.F., Challis G.L., Cherevach I., Chillingworth T., Cronin A.,
RA Crossett B., Davis P., DeShazer D., Feltwell T., Fraser A., Hance Z.,
RA Hauser H., Holroyd S., Jagels K., Keith K.E., Maddison M., Moule S.,
RA Price C., Quail M.A., Rabbinowitsch E., Rutherford K., Sanders M.,
RA Simmonds M., Songsivilai S., Stevens K., Tumapa S., Vesaratchavest M.,
RA Whitehead S., Yeats C., Barrell B.G., Oyston P.C.F., Parkhill J.;
RT "Genomic plasticity of the causative agent of melioidosis, Burkholderia
RT pseudomallei.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14240-14245(2004).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS AND
RP ZINC IONS, COFACTOR, AND SUBUNIT.
RX PubMed=21359640; DOI=10.1007/s10969-011-9102-6;
RA Begley D.W., Hartley R.C., Davies D.R., Edwards T.E., Leonard J.T.,
RA Abendroth J., Burris C.A., Bhandari J., Myler P.J., Staker B.L.,
RA Stewart L.J.;
RT "Leveraging structure determination with fragment screening for infectious
RT disease drug targets: MECP synthase from Burkholderia pseudomallei.";
RL J. Struct. Funct. Genomics 12:63-76(2011).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOGS
RP AND ZINC IONS, COFACTOR, AND SUBUNIT.
RG Seattle structural genomics center for infectious disease (SSGCID);
RA Begley D.W., Edwards T.E., Staker B.L., Hartley R.C., Dieterich M.,
RA Leonard J., Burris C.;
RT "Crystal structure of 2c-methyl-D-erythritol 2,4-cyclodiphosphate synthase
RT from Burkholderia pseudomallei in complex with cytidine derivative
RT EBSI01028.";
RL Submitted (JAN-2011) to the PDB data bank.
CC -!- FUNCTION: Involved in the biosynthesis of isopentenyl diphosphate (IPP)
CC and dimethylallyl diphosphate (DMAPP), two major building blocks of
CC isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-
CC C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol
CC 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine
CC 5-monophosphate (CMP). {ECO:0000255|HAMAP-Rule:MF_00107}.
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_00107};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00107,
CC ECO:0000269|PubMed:21359640, ECO:0000269|Ref.3};
CC Note=Binds 1 divalent metal cation per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_00107, ECO:0000269|PubMed:21359640, ECO:0000269|Ref.3};
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_00107}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000255|HAMAP-Rule:MF_00107,
CC ECO:0000269|PubMed:21359640, ECO:0000269|Ref.3}.
CC -!- SIMILARITY: Belongs to the IspF family. {ECO:0000255|HAMAP-
CC Rule:MF_00107}.
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DR EMBL; BX571965; CAH36101.1; -; Genomic_DNA.
DR RefSeq; WP_004191369.1; NZ_CP009538.1.
DR RefSeq; YP_108695.1; NC_006350.1.
DR PDB; 3IEW; X-ray; 2.10 A; A/B/C=1-162.
DR PDB; 3IKE; X-ray; 2.30 A; A/B/C=1-162.
DR PDB; 3IKF; X-ray; 2.07 A; A/B/C=1-162.
DR PDB; 3Q8H; X-ray; 1.75 A; A/B/C=1-162.
DR PDBsum; 3IEW; -.
DR PDBsum; 3IKE; -.
DR PDBsum; 3IKF; -.
DR PDBsum; 3Q8H; -.
DR AlphaFoldDB; Q63T71; -.
DR SMR; Q63T71; -.
DR STRING; 272560.BPSL2098; -.
DR BindingDB; Q63T71; -.
DR ChEMBL; CHEMBL3091270; -.
DR EnsemblBacteria; CAH36101; CAH36101; BPSL2098.
DR GeneID; 56595885; -.
DR KEGG; bps:BPSL2098; -.
DR PATRIC; fig|272560.51.peg.3381; -.
DR eggNOG; COG0245; Bacteria.
DR OMA; QHFGTGR; -.
DR UniPathway; UPA00056; UER00095.
DR EvolutionaryTrace; Q63T71; -.
DR Proteomes; UP000000605; Chromosome 1.
DR GO; GO:0008685; F:2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase 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; cd00554; MECDP_synthase; 1.
DR Gene3D; 3.30.1330.50; -; 1.
DR HAMAP; MF_00107; IspF; 1.
DR InterPro; IPR003526; MECDP_synthase.
DR InterPro; IPR020555; MECDP_synthase_CS.
DR InterPro; IPR036571; MECDP_synthase_sf.
DR PANTHER; PTHR43181; PTHR43181; 1.
DR Pfam; PF02542; YgbB; 1.
DR SUPFAM; SSF69765; SSF69765; 1.
DR TIGRFAMs; TIGR00151; ispF; 1.
DR PROSITE; PS01350; ISPF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Isoprene biosynthesis; Lyase; Metal-binding;
KW Reference proteome.
FT CHAIN 1..162
FT /note="2-C-methyl-D-erythritol 2,4-cyclodiphosphate
FT synthase"
FT /id="PRO_0000189450"
FT BINDING 10..12
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 10
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 12
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 36..37
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 44
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 58..60
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 63..67
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT BINDING 67
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT BINDING 102..108
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT BINDING 133..137
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT BINDING 144
FT /ligand="4-CDP-2-C-methyl-D-erythritol 2-phosphate"
FT /ligand_id="ChEBI:CHEBI:57919"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT SITE 36
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT SITE 135
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00107"
FT STRAND 2..16
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 25..27
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:3IKE"
FT HELIX 41..53
FT /evidence="ECO:0007829|PDB:3Q8H"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:3Q8H"
FT TURN 69..72
FT /evidence="ECO:0007829|PDB:3Q8H"
FT HELIX 75..88
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 91..101
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:3Q8H"
FT HELIX 108..122
FT /evidence="ECO:0007829|PDB:3Q8H"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:3Q8H"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:3Q8H"
FT STRAND 146..158
FT /evidence="ECO:0007829|PDB:3Q8H"
SQ SEQUENCE 162 AA; 17175 MW; 77F4A6B473C5961C CRC64;
MDFRIGQGYD VHQLVPGRPL IIGGVTIPYE RGLLGHSDAD VLLHAITDAL FGAAALGDIG
RHFSDTDPRF KGADSRALLR ECASRVAQAG FAIRNVDSTI IAQAPKLAPH IDAMRANIAA
DLDLPLDRVN VKAKTNEKLG YLGRGEGIEA QAAALVVREA AA
