ISPE_MYCTU
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 03-AUG-2022, entry version 41.
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; 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 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.m111.011627;
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 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};
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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 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; P9WKG7; -.
DR GeneID; 886034; -.
DR KEGG; mtu:Rv1011; -.
DR TubercuList; Rv1011; -.
DR eggNOG; COG1947; Bacteria.
DR OMA; ACDALWG; -.
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; -; 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_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR43527:SF2; PTHR43527:SF2; 1.
DR Pfam; PF08544; GHMP_kinases_C; 1.
DR Pfam; PF00288; GHMP_kinases_N; 1.
DR PIRSF; PIRSF010376; IspE; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55060; SSF55060; 1.
DR TIGRFAMs; TIGR00154; ispE; 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 6..20
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 31..48
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 53..58
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 71..82
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 89..95
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 105..120
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 168..174
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 181..194
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 203..212
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 215..218
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 227..233
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 236..246
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 258..267
FT /evidence="ECO:0007829|PDB:3PYF"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 283..292
FT /evidence="ECO:0007829|PDB:3PYF"
FT STRAND 297..299
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
