ISPD_MYCTU
ID ISPD_MYCTU Reviewed; 231 AA.
AC P9WKG9; L0TG52; P96864;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 38.
DE RecName: Full=2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase {ECO:0000255|HAMAP-Rule:MF_00108};
DE EC=2.7.7.60 {ECO:0000255|HAMAP-Rule:MF_00108};
DE AltName: Full=4-diphosphocytidyl-2C-methyl-D-erythritol synthase {ECO:0000255|HAMAP-Rule:MF_00108};
DE AltName: Full=MEP cytidylyltransferase {ECO:0000255|HAMAP-Rule:MF_00108};
DE Short=MCT {ECO:0000255|HAMAP-Rule:MF_00108};
GN Name=ispD {ECO:0000255|HAMAP-Rule:MF_00108}; OrderedLocusNames=Rv3582c;
GN ORFNames=MTCY06G11.29c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
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 {ECO:0000255|HAMAP-Rule:MF_00108}.
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_00108};
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_00108}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the IspD/TarI cytidylyltransferase family. IspD
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_00108}.
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DR EMBL; AL123456; CCP46405.1; -; Genomic_DNA.
DR PIR; D70607; D70607.
DR RefSeq; NP_218099.1; NC_000962.3.
DR RefSeq; WP_003419436.1; NZ_NVQJ01000014.1.
DR PDB; 2XWN; X-ray; 2.90 A; A/B=1-229.
DR PDB; 3OKR; X-ray; 2.40 A; A/B/C/D=1-231.
DR PDB; 3Q7U; X-ray; 2.10 A; A/B=2-231.
DR PDB; 3Q80; X-ray; 2.00 A; A/B=2-231.
DR PDBsum; 2XWN; -.
DR PDBsum; 3OKR; -.
DR PDBsum; 3Q7U; -.
DR PDBsum; 3Q80; -.
DR AlphaFoldDB; P9WKG9; -.
DR SMR; P9WKG9; -.
DR STRING; 83332.Rv3582c; -.
DR SwissLipids; SLP:000001165; -.
DR PaxDb; P9WKG9; -.
DR DNASU; 887787; -.
DR GeneID; 45427570; -.
DR GeneID; 887787; -.
DR KEGG; mtu:Rv3582c; -.
DR TubercuList; Rv3582c; -.
DR eggNOG; COG1211; Bacteria.
DR OMA; ERQHSVY; -.
DR PhylomeDB; P9WKG9; -.
DR BRENDA; 2.7.7.60; 3445.
DR UniPathway; UPA00056; UER00093.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0050518; F:2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase activity; IDA:MTBBASE.
DR GO; GO:0002135; F:CTP binding; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR GO; GO:0051484; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway involved in terpenoid biosynthetic process; IDA:MTBBASE.
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; Isoprene biosynthesis; Nucleotidyltransferase;
KW Reference proteome; Transferase.
FT CHAIN 1..231
FT /note="2-C-methyl-D-erythritol 4-phosphate
FT cytidylyltransferase"
FT /id="PRO_0000075592"
FT SITE 20
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00108"
FT SITE 27
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00108"
FT SITE 157
FT /note="Positions MEP for the nucleophilic attack"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00108"
FT SITE 215
FT /note="Positions MEP for the nucleophilic attack"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00108"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:3Q80"
FT TURN 19..21
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 23..25
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 27..29
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 37..47
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 92..94
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3Q7U"
FT STRAND 101..105
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 115..126
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 130..136
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 167..170
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 171..181
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:3Q7U"
FT STRAND 191..193
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 194..199
FT /evidence="ECO:0007829|PDB:3Q80"
FT STRAND 205..208
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:3Q80"
FT HELIX 219..230
FT /evidence="ECO:0007829|PDB:3Q80"
SQ SEQUENCE 231 AA; 24074 MW; 6A4B9549669A0EA0 CRC64;
MVREAGEVVA IVPAAGSGER LAVGVPKAFY QLDGQTLIER AVDGLLDSGV VDTVVVAVPA
DRTDEARQIL GHRAMIVAGG SNRTDTVNLA LTVLSGTAEP EFVLVHDAAR ALTPPALVAR
VVEALRDGYA AVVPVLPLSD TIKAVDANGV VLGTPERAGL RAVQTPQGFT TDLLLRSYQR
GSLDLPAAEY TDDASLVEHI GGQVQVVDGD PLAFKITTKL DLLLAQAIVR G
