FKBO_STRHY
ID FKBO_STRHY Reviewed; 344 AA.
AC Q9KID9;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 56.
DE RecName: Full=Chorismatase {ECO:0000303|PubMed:21383123};
DE EC=3.3.2.13 {ECO:0000269|PubMed:21383123, ECO:0000269|PubMed:24036425};
DE AltName: Full=Chorismate hydrolase {ECO:0000303|PubMed:21383123};
GN Name=fkbO;
OS Streptomyces hygroscopicus.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces; Streptomyces violaceusniger group.
OX NCBI_TaxID=1912;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10863099; DOI=10.1016/s0378-1119(00)00171-2;
RA Wu K., Chung L., Revill W.P., Katz L., Reeves C.D.;
RT "The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus
RT (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender
RT units.";
RL Gene 251:81-90(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21383123; DOI=10.1073/pnas.1015773108;
RA Andexer J.N., Kendrew S.G., Nur-e-Alam M., Lazos O., Foster T.A.,
RA Zimmermann A.S., Warneck T.D., Suthar D., Coates N.J., Koehn F.E.,
RA Skotnicki J.S., Carter G.T., Gregory M.A., Martin C.J., Moss S.J.,
RA Leadlay P.F., Wilkinson B.;
RT "Biosynthesis of the immunosuppressants FK506, FK520, and rapamycin
RT involves a previously undescribed family of enzymes acting on chorismate.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:4776-4781(2011).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.08 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF
RP TYR-215; ARG-228 AND GLU-338, ACTIVITY REGULATION, ACTIVE SITE, REACTION
RP MECHANISM, AND SUBUNIT.
RX PubMed=24036425; DOI=10.1016/j.jmb.2013.09.006;
RA Juneja P., Hubrich F., Diederichs K., Welte W., Andexer J.N.;
RT "Mechanistic implications for the chorismatase FkbO based on the crystal
RT structure.";
RL J. Mol. Biol. 426:105-115(2014).
CC -!- FUNCTION: Involved in the biosynthesis of the macrocyclic amino acid-
CC linked polyketides FK506 and FK520 which are potent immunosuppressants
CC that prevent T-cell proliferation through initial binding to the
CC immunophilin FKBP12. Catalyzes the hydrolysis of chorismate via a 1,4-
CC conjugate elimination of water to yield (4R,5R)-4,5-dihydroxycyclohexa-
CC 1,5-dienecarboxylic acid (DCDC). {ECO:0000269|PubMed:21383123,
CC ECO:0000269|PubMed:24036425}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chorismate + H2O = (3R,4R)-3,4-dihydroxy-3,4-dihydrobenzoate +
CC pyruvate; Xref=Rhea:RHEA:38319, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:29748, ChEBI:CHEBI:75717; EC=3.3.2.13;
CC Evidence={ECO:0000269|PubMed:21383123, ECO:0000269|PubMed:24036425};
CC -!- ACTIVITY REGULATION: Competitively inhibited by 3-(2-
CC carboxyethyl)benzoate. {ECO:0000269|PubMed:24036425}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.15 mM for chorismate {ECO:0000269|PubMed:24036425};
CC KM=0.2 mM for chorismate {ECO:0000269|PubMed:21383123};
CC Vmax=0.56 umol/min/mg enzyme {ECO:0000269|PubMed:24036425};
CC Note=kcat is 17.6 sec(-1) for chorismatase activity with chorismate
CC as substrate. {ECO:0000269|PubMed:21383123};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:24036425}.
CC -!- SIMILARITY: Belongs to the FkbO/Hyg5 family. {ECO:0000305}.
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DR EMBL; AF235504; AAF86394.1; -; Genomic_DNA.
DR PDB; 4BPS; X-ray; 1.08 A; A=1-344.
DR PDBsum; 4BPS; -.
DR AlphaFoldDB; Q9KID9; -.
DR SMR; Q9KID9; -.
DR ChEMBL; CHEMBL2331069; -.
DR KEGG; ag:AAF86394; -.
DR BRENDA; 3.3.2.13; 6043.
DR GO; GO:0016803; F:ether hydrolase activity; IDA:UniProtKB.
DR Gene3D; 3.30.1330.40; -; 1.
DR InterPro; IPR031038; Chori_FkbO_Hyg5.
DR InterPro; IPR035959; RutC-like_sf.
DR SUPFAM; SSF55298; SSF55298; 1.
DR TIGRFAMs; TIGR04444; chori_FkbO_Hyg5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase.
FT CHAIN 1..344
FT /note="Chorismatase"
FT /id="PRO_0000435462"
FT ACT_SITE 338
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:24036425"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24036425"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24036425"
FT BINDING 215
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24036425"
FT BINDING 228
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:24036425"
FT MUTAGEN 215
FT /note="Y->F: Decrease of the affinity for chorismate."
FT /evidence="ECO:0000269|PubMed:24036425"
FT MUTAGEN 228
FT /note="R->A: Same activity as the wild-type."
FT /evidence="ECO:0000269|PubMed:24036425"
FT MUTAGEN 338
FT /note="E->A: Loss of chorismatase activity."
FT /evidence="ECO:0000269|PubMed:24036425"
FT MUTAGEN 338
FT /note="E->Q: Loss of chorismatase activity."
FT /evidence="ECO:0000269|PubMed:24036425"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 68..70
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 96..105
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 112..129
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 133..142
FT /evidence="ECO:0007829|PDB:4BPS"
FT TURN 143..145
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 154..169
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 173..175
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 178..199
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 217..219
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:4BPS"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 239..250
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 259..274
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 276..281
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 294..301
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:4BPS"
FT HELIX 306..314
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 323..327
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 330..332
FT /evidence="ECO:0007829|PDB:4BPS"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:4BPS"
SQ SEQUENCE 344 AA; 36947 MW; A171E5816CAAC980 CRC64;
MTDAGRQGRV EALSISVTAP YCRFEKTGSP DLEGDETVLG LIEHGTGHTD VSLVDGAPRT
AVHTTTRDDE AFTEVWHAQR PVESGMDNGI AWARTDAYLF GVVRTGESGR YADATAALYT
NVFQLTRSLG YPLLARTWNY VSGINTTNAD GLEVYRDFCV GRAQALDEGG IDPATMPAAT
GIGAHGGGIT CVFLAARGGV RINIENPAVL TAHHYPTTYG PRPPVFARAT WLGPPEGGRL
FISATAGILG HRTVHHGDVT GQCEVALDNM ARVIGAENLR RHGVQRGHVL ADVDHLKVYV
RRREDLDTVR RVCAARLSST AAVALLHTDI AREDLLVEIE GMVA
