AROB_MYCTU
ID AROB_MYCTU Reviewed; 362 AA.
AC P9WPX9; L0TCN7; P0A4Z4; P36919; P95015;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=3-dehydroquinate synthase {ECO:0000255|HAMAP-Rule:MF_00110};
DE Short=DHQS {ECO:0000255|HAMAP-Rule:MF_00110};
DE EC=4.2.3.4 {ECO:0000255|HAMAP-Rule:MF_00110};
GN Name=aroB {ECO:0000255|HAMAP-Rule:MF_00110}; OrderedLocusNames=Rv2538c;
GN ORFNames=MTCY159.18;
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 [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=1910148; DOI=10.1007/bf00260631;
RA Garbe T., Servos S., Hawkins A., Dimitriadis G., Young D., Dougan G.,
RA Charles I.G.;
RT "The Mycobacterium tuberculosis shikimate pathway genes: evolutionary
RT relationship between biosynthetic and catabolic 3-dehydroquinases.";
RL Mol. Gen. Genet. 228:385-392(1991).
RN [2]
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 [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).
RN [5] {ECO:0007744|PDB:3QBD}
RP X-RAY CRYSTALLOGRAPHY (2.47 ANGSTROMS) IN COMPLEX WITH NAD.
RA Cheng W.C., Chen T.J., Wang W.C.;
RT "3-dehydroquinate synthase (aroB) from Mycobacterium tuberculosis in
RT complex with NAD.";
RL Submitted (JAN-2011) to the PDB data bank.
RN [6] {ECO:0007744|PDB:3QBE}
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) IN COMPLEX WITH ZINC.
RA Cheng W.C., Chen T.J., Wang W.C.;
RT "Crystal structure of the 3-dehydroquinate synthase (aroB) from
RT Mycobacterium tuberculosis.";
RL Submitted (JAN-2011) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the conversion of 3-deoxy-D-arabino-heptulosonate
CC 7-phosphate (DAHP) to dehydroquinate (DHQ). {ECO:0000255|HAMAP-
CC Rule:MF_00110}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-phospho-2-dehydro-3-deoxy-D-arabino-heptonate = 3-
CC dehydroquinate + phosphate; Xref=Rhea:RHEA:21968, ChEBI:CHEBI:32364,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58394; EC=4.2.3.4;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00110};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00110};
CC -!- COFACTOR:
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00110};
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00110};
CC Note=Binds 1 divalent metal cation per subunit. Can use either Co(2+)
CC or Zn(2+). {ECO:0000255|HAMAP-Rule:MF_00110};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis;
CC chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate: step
CC 2/7. {ECO:0000255|HAMAP-Rule:MF_00110}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00110}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the sugar phosphate cyclases superfamily.
CC Dehydroquinate synthase family. {ECO:0000255|HAMAP-Rule:MF_00110,
CC ECO:0000305}.
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DR EMBL; X59509; CAA42095.1; -; Genomic_DNA.
DR EMBL; AL123456; CCP45333.1; -; Genomic_DNA.
DR PIR; S17768; S17768.
DR RefSeq; NP_217054.1; NC_000962.3.
DR RefSeq; WP_003413008.1; NZ_NVQJ01000032.1.
DR PDB; 3QBD; X-ray; 2.47 A; A/B=1-362.
DR PDB; 3QBE; X-ray; 2.07 A; A=1-362.
DR PDBsum; 3QBD; -.
DR PDBsum; 3QBE; -.
DR AlphaFoldDB; P9WPX9; -.
DR SMR; P9WPX9; -.
DR STRING; 83332.Rv2538c; -.
DR PaxDb; P9WPX9; -.
DR DNASU; 888392; -.
DR GeneID; 888392; -.
DR KEGG; mtu:Rv2538c; -.
DR TubercuList; Rv2538c; -.
DR eggNOG; COG0337; Bacteria.
DR OMA; YGVIWDA; -.
DR PhylomeDB; P9WPX9; -.
DR BRENDA; 4.2.3.4; 3445.
DR Reactome; R-MTU-964903; Chorismate via Shikimate Pathway.
DR UniPathway; UPA00053; UER00085.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003856; F:3-dehydroquinate synthase activity; IMP:MTBBASE.
DR GO; GO:0005507; F:copper ion binding; IDA:MTBBASE.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR GO; GO:0009073; P:aromatic amino acid family biosynthetic process; IMP:MTBBASE.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009423; P:chorismate biosynthetic process; TAS:Reactome.
DR HAMAP; MF_00110; DHQ_synthase; 1.
DR InterPro; IPR016037; DHQ_synth_AroB.
DR InterPro; IPR030963; DHQ_synth_fam.
DR InterPro; IPR030960; DHQS/DOIS.
DR Pfam; PF01761; DHQ_synthase; 1.
DR PIRSF; PIRSF001455; DHQ_synth; 1.
DR TIGRFAMs; TIGR01357; aroB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Aromatic amino acid biosynthesis;
KW Cobalt; Cytoplasm; Lyase; Metal-binding; NAD; Nucleotide-binding;
KW Reference proteome; Zinc.
FT CHAIN 1..362
FT /note="3-dehydroquinate synthase"
FT /id="PRO_0000140757"
FT BINDING 45
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 73..78
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 107..111
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 131..132
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 144
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 153
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q6GGU4, ECO:0000255|HAMAP-
FT Rule:MF_00110"
FT BINDING 171..174
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0000269|Ref.5, ECO:0007744|PDB:3QBD"
FT BINDING 186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0007744|PDB:3QBE"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0007744|PDB:3QBE"
FT BINDING 265
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00110,
FT ECO:0007744|PDB:3QBE"
FT CONFLICT 99
FT /note="D -> N (in Ref. 1; CAA42095)"
FT /evidence="ECO:0000305"
FT STRAND 8..12
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 18..24
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 27..34
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 49..61
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 74..78
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 80..93
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 107..119
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 125..130
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 133..137
FT /evidence="ECO:0007829|PDB:3QBE"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 152..159
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 169..174
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 177..193
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 196..204
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 206..209
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:3QBD"
FT HELIX 216..233
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 241..246
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:3QBE"
FT TURN 259..261
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 265..282
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 312..320
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:3QBE"
FT STRAND 341..346
FT /evidence="ECO:0007829|PDB:3QBE"
FT HELIX 349..360
FT /evidence="ECO:0007829|PDB:3QBE"
SQ SEQUENCE 362 AA; 38119 MW; DDE0C08FFF978F1A CRC64;
MTDIGAPVTV QVAVDPPYPV VIGTGLLDEL EDLLADRHKV AVVHQPGLAE TAEEIRKRLA
GKGVDAHRIE IPDAEAGKDL PVVGFIWEVL GRIGIGRKDA LVSLGGGAAT DVAGFAAATW
LRGVSIVHLP TTLLGMVDAA VGGKTGINTD AGKNLVGAFH QPLAVLVDLA TLQTLPRDEM
ICGMAEVVKA GFIADPVILD LIEADPQAAL DPAGDVLPEL IRRAITVKAE VVAADEKESE
LREILNYGHT LGHAIERRER YRWRHGAAVS VGLVFAAELA RLAGRLDDAT AQRHRTILSS
LGLPVSYDPD ALPQLLEIMA GDKKTRAGVL RFVVLDGLAK PGRMVGPDPG LLVTAYAGVC
AP
