ID ISPE_MYCTU Reviewed; 318 AA.
AC P9WKG7; L0T5K3; O05596; P65178;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 2.
DT 08-NOV-2023, entry version 48.
DE RecName: Full=4-diphosphocytidyl-2-C-methyl-D-erythritol kinase {ECO:0000255|HAMAP-Rule:MF_00061};
DE Short=CMK {ECO:0000255|HAMAP-Rule:MF_00061};
DE EC=2.7.1.148 {ECO:0000255|HAMAP-Rule:MF_00061};
DE AltName: Full=4-(cytidine-5'-diphospho)-2-C-methyl-D-erythritol kinase {ECO:0000255|HAMAP-Rule:MF_00061};
DE Contains:
DE RecName: Full=4-diphosphocytidyl-2-C-methyl-D-erythritol kinase, propeptide removed;
GN Name=ispE {ECO:0000255|HAMAP-Rule:MF_00061}; OrderedLocusNames=Rv1011;
GN ORFNames=MTCI237.28;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; 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 PROTEIN SEQUENCE OF 2-25, PROTEIN SEQUENCE OF 3-25, AND SEQUENCE REVISION
RP TO N-TERMINUS.
RC STRAIN=H37Rv;
RX PubMed=34915127; DOI=10.1016/j.ygeno.2021.12.001;
RA Shi J., Meng S., Wan L., Zhang Z., Jiang S., Zhu H., Dai E., Chang L.,
RA Gao H., Wan K., Zhang L., Zhao X., Liu H., Lyu Z., Zhang Y., Xu P.;
RT "Deep N-terminomics of Mycobacterium tuberculosis H37Rv extensively correct
RT annotated encoding genes.";
RL Genomics 114:292-304(2022).
RN [3]
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011445;
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 phosphorylation of the position 2 hydroxy group
CC of 4-diphosphocytidyl-2C-methyl-D-erythritol. {ECO:0000255|HAMAP-
CC Rule:MF_00061}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-CDP-2-C-methyl-D-erythritol + ATP = 4-CDP-2-C-methyl-D-
CC erythritol 2-phosphate + ADP + H(+); Xref=Rhea:RHEA:18437,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:57823,
CC ChEBI:CHEBI:57919, ChEBI:CHEBI:456216; EC=2.7.1.148;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00061};
CC -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC via DXP pathway; isopentenyl diphosphate from 1-deoxy-D-xylulose 5-
CC phosphate: step 3/6. {ECO:0000255|HAMAP-Rule:MF_00061}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the GHMP kinase family. IspE subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_00061}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CCP43761.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000269|PubMed:34915127};
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; AL123456; CCP43761.1; ALT_INIT; Genomic_DNA.
DR PIR; F70603; F70603.
DR RefSeq; NP_215527.1; NC_000962.3.
DR RefSeq; WP_003405199.1; NC_000962.3.
DR RefSeq; WP_003898690.1; NZ_NVQJ01000018.1.
DR PDB; 3PYD; X-ray; 2.10 A; A=17-314.
DR PDB; 3PYE; X-ray; 2.00 A; A=13-313.
DR PDB; 3PYF; X-ray; 1.70 A; A=17-312.
DR PDB; 3PYG; X-ray; 1.99 A; A=16-313.
DR PDBsum; 3PYD; -.
DR PDBsum; 3PYE; -.
DR PDBsum; 3PYF; -.
DR PDBsum; 3PYG; -.
DR AlphaFoldDB; P9WKG7; -.
DR SMR; P9WKG7; -.
DR STRING; 83332.Rv1011; -.
DR PaxDb; 83332-Rv1011; -.
DR GeneID; 45424983; -.
DR GeneID; 886034; -.
DR KEGG; mtu:Rv1011; -.
DR TubercuList; Rv1011; -.
DR eggNOG; COG1947; Bacteria.
DR InParanoid; P9WKG7; -.
DR OrthoDB; 3173073at2; -.
DR PhylomeDB; P9WKG7; -.
DR BRENDA; 2.7.1.148; 3445.
DR UniPathway; UPA00056; UER00094.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0050515; F:4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol kinase activity; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0019288; P:isopentenyl diphosphate biosynthetic process, methylerythritol 4-phosphate pathway; IEA:UniProtKB-UniPathway.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniRule.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.70.890; GHMP kinase, C-terminal domain; 1.
DR HAMAP; MF_00061; IspE; 1.
DR InterPro; IPR013750; GHMP_kinase_C_dom.
DR InterPro; IPR036554; GHMP_kinase_C_sf.
DR InterPro; IPR006204; GHMP_kinase_N_dom.
DR InterPro; IPR004424; IspE.
DR InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF.
DR InterPro; IPR014721; Ribsml_uS5_D2-typ_fold_subgr.
DR NCBIfam; TIGR00154; ispE; 1.
DR PANTHER; PTHR43527; 4-DIPHOSPHOCYTIDYL-2-C-METHYL-D-ERYTHRITOL KINASE, CHLOROPLASTIC; 1.
DR PANTHER; PTHR43527:SF2; 4-DIPHOSPHOCYTIDYL-2-C-METHYL-D-ERYTHRITOL KINASE, CHLOROPLASTIC; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR PIRSF; PIRSF010376; IspE; 1.
DR SUPFAM; SSF55060; GHMP Kinase, C-terminal domain; 1.
DR SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Direct protein sequencing;
KW Isoprene biosynthesis; Kinase; Nucleotide-binding; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:34915127"
FT CHAIN 2..318
FT /note="4-diphosphocytidyl-2-C-methyl-D-erythritol kinase"
FT /id="PRO_0000189235"
FT PROPEP 2
FT /note="Removed; alternate"
FT /evidence="ECO:0000269|PubMed:34915127"
FT /id="PRO_0000455339"
FT CHAIN 3..318
FT /note="4-diphosphocytidyl-2-C-methyl-D-erythritol kinase,
FT propeptide removed"
FT /id="PRO_0000455340"
FT ACT_SITE 25
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00061"
FT ACT_SITE 152
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00061"
FT BINDING 110..120
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00061"
FT STRAND 18..32
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 43..60
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 73..75
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 83..94
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 101..107
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 117..132
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 139..149
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 153..158
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 159..164
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 193..206
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 227..230
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 239..245
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 248..258
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 262..266
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 280..292
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 295..304
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 309..311
FT /evidence="ECO:0007829|PDB:3PYF"
SQ SEQUENCE 318 AA; 32613 MW; D3599C4B63EA3461 CRC64;
MSASDGNTAE LWVPTGSVTV RVPGKVNLYL AVGDRREDGY HELTTVFHAV SLVDEVTVRN
ADVLSLELVG EGADQLPTDE RNLAWQAAEL MAEHVGRAPD VSIMIDKSIP VAGGMAGGSA
DAAAVLVAMN SLWELNVPRR DLRMLAARLG SDVPFALHGG TALGTGRGEE LATVLSRNTF
HWVLAFADSG LLTSAVYNEL DRLREVGDPP RLGEPGPVLA ALAAGDPDQL APLLGNEMQA
AAVSLDPALA RALRAGVEAG ALAGIVSGSG PTCAFLCTSA SSAIDVGAQL SGAGVCRTVR
VATGPVPGAR VVSAPTEV
//
