AROC_MYCTU
ID AROC_MYCTU Reviewed; 401 AA.
AC P9WPY1; L0T9X6; P63611; P95013;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Chorismate synthase {ECO:0000255|HAMAP-Rule:MF_00300};
DE Short=CS {ECO:0000255|HAMAP-Rule:MF_00300, ECO:0000303|PubMed:16459102};
DE EC=4.2.3.5 {ECO:0000255|HAMAP-Rule:MF_00300};
DE AltName: Full=5-enolpyruvylshikimate-3-phosphate phospholyase {ECO:0000255|HAMAP-Rule:MF_00300};
GN Name=aroC {ECO:0000255|HAMAP-Rule:MF_00300}; Synonyms=aroF;
GN OrderedLocusNames=Rv2540c; ORFNames=MTCY159.16;
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).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS), AND SUBUNIT.
RX PubMed=16459102; DOI=10.1016/j.jsb.2005.12.008;
RA Dias M.V., Borges J.C., Ely F., Pereira J.H., Canduri F., Ramos C.H.,
RA Frazzon J., Palma M.S., Basso L.A., Santos D.S., de Azevedo W.F. Jr.;
RT "Structure of chorismate synthase from Mycobacterium tuberculosis.";
RL J. Struct. Biol. 154:130-143(2006).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.22 ANGSTROMS).
RA Dias M.V.B., Dos Santos B.B., Ely F., Basso L.A., Santos D.S.,
RA de Azevedo W.F. Jr.;
RT "Crystal structure of chorismate synthase from mycobacterium tuberculosis
RT at 2.22 angstroms of resolution.";
RL Submitted (MAR-2007) to the PDB data bank.
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH NADP ANALOG; FMN,
RP AND COFACTOR.
RA Bruning M., Bourenkov G.P., Strizhov N.I., Bartunik H.D.;
RT "Mycobacterium tuberculosis chorismate synthase in complex with NCA and
RT FMN.";
RL Submitted (JUL-2008) to the PDB data bank.
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS).
RX PubMed=23178456; DOI=10.1016/j.jsb.2012.11.003;
RA Pereira P.J., Royant A., Panjikar S., de Sanctis D.;
RT "In-house UV radiation-damage-induced phasing of selenomethionine-labeled
RT protein structures.";
RL J. Struct. Biol. 181:89-94(2013).
CC -!- FUNCTION: Catalyzes the anti-1,4-elimination of the C-3 phosphate and
CC the C-6 proR hydrogen from 5-enolpyruvylshikimate-3-phosphate (EPSP) to
CC yield chorismate, which is the branch point compound that serves as the
CC starting substrate for the three terminal pathways of aromatic amino
CC acid biosynthesis. This reaction introduces a second double bond into
CC the aromatic ring system. {ECO:0000255|HAMAP-Rule:MF_00300}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-O-(1-carboxyvinyl)-3-phosphoshikimate = chorismate +
CC phosphate; Xref=Rhea:RHEA:21020, ChEBI:CHEBI:29748,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57701; EC=4.2.3.5;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00300};
CC -!- COFACTOR:
CC Name=FMNH2; Xref=ChEBI:CHEBI:57618;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_00300, ECO:0000269|Ref.6};
CC Note=Reduced FMN (FMNH(2)). {ECO:0000255|HAMAP-Rule:MF_00300,
CC ECO:0000269|Ref.6};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; chorismate biosynthesis;
CC chorismate from D-erythrose 4-phosphate and phosphoenolpyruvate: step
CC 7/7. {ECO:0000255|HAMAP-Rule:MF_00300}.
CC -!- SUBUNIT: Homotetramer: dimer of dimers. {ECO:0000255|HAMAP-
CC Rule:MF_00300, ECO:0000269|PubMed:16459102}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the chorismate synthase family.
CC {ECO:0000255|HAMAP-Rule:MF_00300}.
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DR EMBL; AL123456; CCP45335.1; -; Genomic_DNA.
DR PIR; H70658; H70658.
DR RefSeq; NP_217056.1; NC_000962.3.
DR RefSeq; WP_003413027.1; NZ_NVQJ01000032.1.
DR PDB; 1ZTB; X-ray; 2.65 A; A=1-401.
DR PDB; 2G85; X-ray; 2.22 A; A=1-401.
DR PDB; 2O11; X-ray; 1.65 A; A=1-401.
DR PDB; 2O12; X-ray; 1.72 A; A=1-401.
DR PDB; 2QHF; X-ray; 1.65 A; A=1-401.
DR PDB; 4BAI; X-ray; 2.30 A; A=1-401.
DR PDB; 4BAJ; X-ray; 2.30 A; A=1-401.
DR PDBsum; 1ZTB; -.
DR PDBsum; 2G85; -.
DR PDBsum; 2O11; -.
DR PDBsum; 2O12; -.
DR PDBsum; 2QHF; -.
DR PDBsum; 4BAI; -.
DR PDBsum; 4BAJ; -.
DR AlphaFoldDB; P9WPY1; -.
DR SMR; P9WPY1; -.
DR STRING; 83332.Rv2540c; -.
DR PaxDb; P9WPY1; -.
DR GeneID; 887379; -.
DR KEGG; mtu:Rv2540c; -.
DR TubercuList; Rv2540c; -.
DR eggNOG; COG0082; Bacteria.
DR OMA; MLSINAV; -.
DR PhylomeDB; P9WPY1; -.
DR Reactome; R-MTU-964903; Chorismate via Shikimate Pathway.
DR UniPathway; UPA00053; UER00090.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0004107; F:chorismate synthase activity; IDA:MTBBASE.
DR GO; GO:0010181; F:FMN binding; IDA:MTBBASE.
DR GO; GO:0051287; F:NAD binding; IDA:MTBBASE.
DR GO; GO:0016651; F:oxidoreductase activity, acting on NAD(P)H; IDA:MTBBASE.
DR GO; GO:0009073; P:aromatic amino acid family biosynthetic process; IBA:GO_Central.
DR GO; GO:0008652; P:cellular amino acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009423; P:chorismate biosynthetic process; IBA:GO_Central.
DR CDD; cd07304; Chorismate_synthase; 1.
DR Gene3D; 3.60.150.10; -; 1.
DR HAMAP; MF_00300; Chorismate_synth; 1.
DR InterPro; IPR000453; Chorismate_synth.
DR InterPro; IPR035904; Chorismate_synth_AroC_sf.
DR InterPro; IPR020541; Chorismate_synthase_CS.
DR PANTHER; PTHR21085; PTHR21085; 1.
DR Pfam; PF01264; Chorismate_synt; 1.
DR PIRSF; PIRSF001456; Chorismate_synth; 1.
DR SUPFAM; SSF103263; SSF103263; 1.
DR TIGRFAMs; TIGR00033; aroC; 1.
DR PROSITE; PS00787; CHORISMATE_SYNTHASE_1; 1.
DR PROSITE; PS00788; CHORISMATE_SYNTHASE_2; 1.
DR PROSITE; PS00789; CHORISMATE_SYNTHASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis; Aromatic amino acid biosynthesis;
KW FAD; Flavoprotein; FMN; Lyase; NADP; Reference proteome.
FT CHAIN 1..401
FT /note="Chorismate synthase"
FT /id="PRO_0000140615"
FT BINDING 40
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300,
FT ECO:0000269|Ref.6"
FT BINDING 46
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300,
FT ECO:0000269|Ref.6"
FT BINDING 135..137
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300"
FT BINDING 256..257
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300,
FT ECO:0000269|Ref.6"
FT BINDING 300
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300"
FT BINDING 315..319
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300,
FT ECO:0000269|Ref.6"
FT BINDING 341
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_00300,
FT ECO:0000269|Ref.6"
FT STRAND 3..7
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 12..21
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:1ZTB"
FT HELIX 30..40
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:2QHF"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:2O12"
FT STRAND 57..64
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 67..71
FT /evidence="ECO:0007829|PDB:1ZTB"
FT STRAND 73..78
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 82..85
FT /evidence="ECO:0007829|PDB:2O11"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 96..100
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 103..105
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 117..124
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 130..136
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 141..159
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 162..170
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 183..185
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 186..191
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:2G85"
FT HELIX 199..215
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 221..229
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 274..277
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 289..291
FT /evidence="ECO:0007829|PDB:2QHF"
FT TURN 294..297
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 308..314
FT /evidence="ECO:0007829|PDB:2O11"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 325..327
FT /evidence="ECO:0007829|PDB:2O11"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:2O11"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 347..370
FT /evidence="ECO:0007829|PDB:2O11"
FT HELIX 375..390
FT /evidence="ECO:0007829|PDB:2O11"
SQ SEQUENCE 401 AA; 41792 MW; 6A3C14761261ADEF CRC64;
MLRWITAGES HGRALVAVVE GMVAGVHVTS ADIADQLARR RLGYGRGARM TFERDAVTVL
SGIRHGSTLG GPIAIEIGNT EWPKWETVMA ADPVDPAELA DVARNAPLTR PRPGHADYAG
MLKYGFDDAR PVLERASARE TAARVAAGTV ARAFLRQALG VEVLSHVISI GASAPYEGPP
PRAEDLPAID ASPVRAYDKA AEADMIAQIE AAKKDGDTLG GVVEAVALGL PVGLGSFTSG
DHRLDSQLAA AVMGIQAIKG VEIGDGFQTA RRRGSRAHDE MYPGPDGVVR STNRAGGLEG
GMTNGQPLRV RAAMKPISTV PRALATVDLA TGDEAVAIHQ RSDVCAVPAA GVVVETMVAL
VLARAALEKF GGDSLAETQR NIAAYQRSVA DREAPAARVS G
