PABB_ECOLI
ID PABB_ECOLI Reviewed; 453 AA.
AC P05041;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 13-AUG-1987, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Aminodeoxychorismate synthase component 1;
DE Short=ADC synthase;
DE Short=ADCS;
DE EC=2.6.1.85;
DE AltName: Full=4-amino-4-deoxychorismate synthase component 1;
GN Name=pabB; OrderedLocusNames=b1812, JW1801;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6330050; DOI=10.1128/jb.159.1.57-62.1984;
RA Goncharoff P., Nichols B.P.;
RT "Nucleotide sequence of Escherichia coli pabB indicates a common
RT evolutionary origin of p-aminobenzoate synthetase and anthranilate
RT synthetase.";
RL J. Bacteriol. 159:57-62(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=9097040; DOI=10.1093/dnares/3.6.379;
RA Itoh T., Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K.,
RA Kasai H., Kimura S., Kitakawa M., Kitagawa M., Makino K., Miki T.,
RA Mizobuchi K., Mori H., Mori T., Motomura K., Nakade S., Nakamura Y.,
RA Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G., Seki Y.,
RA Sivasundaram S., Tagami H., Takeda J., Takemoto K., Wada C., Yamamoto Y.,
RA Horiuchi T.;
RT "A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to
RT the 40.1-50.0 min region on the linkage map.";
RL DNA Res. 3:379-392(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 42-377.
RC STRAIN=ECOR 10, ECOR 16, and ECOR 8;
RX PubMed=7896119; DOI=10.1093/genetics/138.4.993;
RA Guttman D.S., Dykhuizen D.E.;
RT "Detecting selective sweeps in naturally occurring Escherichia coli.";
RL Genetics 138:993-1003(1994).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND NOMENCLATURE.
RX PubMed=4914080; DOI=10.1128/jb.102.3.767-773.1970;
RA Huang M., Gibson F.;
RT "Biosynthesis of 4-aminobenzoate in Escherichia coli.";
RL J. Bacteriol. 102:767-773(1970).
RN [7]
RP PROTEIN SEQUENCE OF 1-12, FUNCTION, CATALYTIC ACTIVITY, AND COFACTOR.
RX PubMed=2251281; DOI=10.1073/pnas.87.23.9391;
RA Ye Q.-Z., Liu J., Walsh C.T.;
RT "p-aminobenzoate synthesis in Escherichia coli: purification and
RT characterization of PabB as aminodeoxychorismate synthase and enzyme X as
RT aminodeoxychorismate lyase.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:9391-9395(1990).
RN [8]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RX PubMed=7592344; DOI=10.1128/jb.177.20.5918-5923.1995;
RA Viswanathan V.K., Green J.M., Nichols B.P.;
RT "Kinetic characterization of 4-amino 4-deoxychorismate synthase from
RT Escherichia coli.";
RL J. Bacteriol. 177:5918-5923(1995).
RN [9]
RP MUTAGENESIS OF GLY-275; ARG-311; ARG-316; SER-322 AND HIS-339, AND SUBUNIT.
RX PubMed=8679677; DOI=10.1016/0167-4838(96)00029-5;
RA Rayl E.A., Green J.M., Nichols B.P.;
RT "Escherichia coli aminodeoxychorismate synthase: analysis of pabB mutations
RT affecting catalysis and subunit association.";
RL Biochim. Biophys. Acta 1295:81-88(1996).
RN [10]
RP MUTAGENESIS OF LYS-274, REACTION MECHANISM, ACTIVE SITE, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14982443; DOI=10.1021/ja0389927;
RA He Z., Stigers Lavoie K.D., Bartlett P.A., Toney M.D.;
RT "Conservation of mechanism in three chorismate-utilizing enzymes.";
RL J. Am. Chem. Soc. 126:2378-2385(2004).
RN [11]
RP ACTIVITY REGULATION.
RX PubMed=15303852; DOI=10.1021/ja048312f;
RA Bulloch E.M., Jones M.A., Parker E.J., Osborne A.P., Stephens E.,
RA Davies G.M., Coggins J.R., Abell C.;
RT "Identification of 4-amino-4-deoxychorismate synthase as the molecular
RT target for the antimicrobial action of (6s)-6-fluoroshikimate.";
RL J. Am. Chem. Soc. 126:9912-9913(2004).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-258 AND LYS-274, REACTION
RP MECHANISM, ACTIVE SITE, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=16605270; DOI=10.1021/bi052216p;
RA He Z., Toney M.D.;
RT "Direct detection and kinetic analysis of covalent intermediate formation
RT in the 4-amino-4-deoxychorismate synthase catalyzed reaction.";
RL Biochemistry 45:5019-5028(2006).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH TRYPTOPHAN, ACTIVE
RP SITE, AND SUBUNIT.
RX PubMed=11841211; DOI=10.1021/bi015791b;
RA Parsons J.F., Jensen P.Y., Pachikara A.S., Howard A.J., Eisenstein E.,
RA Ladner J.E.;
RT "Structure of Escherichia coli aminodeoxychorismate synthase: architectural
RT conservation and diversity in chorismate-utilizing enzymes.";
RL Biochemistry 41:2198-2208(2002).
CC -!- FUNCTION: Part of a heterodimeric complex that catalyzes the two-step
CC biosynthesis of 4-amino-4-deoxychorismate (ADC), a precursor of p-
CC aminobenzoate (PABA) and tetrahydrofolate. In the first step, a
CC glutamine amidotransferase (PabA) generates ammonia as a substrate
CC that, along with chorismate, is used in the second step, catalyzed by
CC aminodeoxychorismate synthase (PabB) to produce ADC. PabB, in the
CC absence of PabA, can catalyze the formation of ADC in the presence of
CC exogenous ammonia. {ECO:0000269|PubMed:16605270,
CC ECO:0000269|PubMed:2251281, ECO:0000269|PubMed:4914080}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chorismate + L-glutamine = 4-amino-4-deoxychorismate + L-
CC glutamate; Xref=Rhea:RHEA:11672, ChEBI:CHEBI:29748,
CC ChEBI:CHEBI:29985, ChEBI:CHEBI:58359, ChEBI:CHEBI:58406; EC=2.6.1.85;
CC Evidence={ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:2251281};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:2251281};
CC -!- ACTIVITY REGULATION: Inhibited by 6-diazo-5-oxo-L-norleucine (DON). The
CC inhibition is competitive with glutamine but uncompetitive with
CC chorismate. Also inhibited by 2-fluorochorismate.
CC {ECO:0000269|PubMed:15303852, ECO:0000269|PubMed:7592344}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.2 uM for chorismate (with PabA and glutamine as the amino donor
CC at pH 7.5) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270,
CC ECO:0000269|PubMed:7592344};
CC KM=18.6 uM for chorismate (with PabA and ammonia as the amino donor
CC at pH 7.5) {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270,
CC ECO:0000269|PubMed:7592344};
CC KM=71 uM for chorismate {ECO:0000269|PubMed:14982443,
CC ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344};
CC KM=75 uM for chorismate (with PabA) {ECO:0000269|PubMed:14982443,
CC ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344};
CC KM=379 uM for chorismate (with PabA and ammonia)
CC {ECO:0000269|PubMed:14982443, ECO:0000269|PubMed:16605270,
CC ECO:0000269|PubMed:7592344};
CC KM=388 uM for chorismate (with ammonia) {ECO:0000269|PubMed:14982443,
CC ECO:0000269|PubMed:16605270, ECO:0000269|PubMed:7592344};
CC -!- PATHWAY: Cofactor biosynthesis; tetrahydrofolate biosynthesis; 4-
CC aminobenzoate from chorismate: step 1/2.
CC -!- SUBUNIT: Monomer. Heterodimer consisting of two non-identical subunits:
CC a glutamine amidotransferase subunit (PabA) and a aminodeoxychorismate
CC synthase subunit (PabB). {ECO:0000269|PubMed:11841211,
CC ECO:0000269|PubMed:8679677}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene do not produce 4-
CC aminobenzoate. {ECO:0000269|PubMed:4914080}.
CC -!- MISCELLANEOUS: In this enzymatic reaction the C4 hydroxy group of
CC chorismate is replaced by addition of a nucleophile at the C2 position.
CC The nucleophile is the epsilon-amino group of lysine 274 transiently
CC binds to C2 of chorismate (PubMed:16605270). PabB contains a tryptophan
CC (Trp) molecule deeply embedded in a binding pocket. Trp which cannot be
CC dissociated without denaturation of PabB, may play a structural role in
CC the enzyme since it has no effect on the enzymic synthesis of
CC aminodeoxychorismate (PubMed:11841211). {ECO:0000305|PubMed:11841211,
CC ECO:0000305|PubMed:16605270}.
CC -!- SIMILARITY: Belongs to the anthranilate synthase component I family.
CC {ECO:0000305}.
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DR EMBL; K02673; AAA24266.1; -; Genomic_DNA.
DR EMBL; U00096; AAC74882.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA15619.1; -; Genomic_DNA.
DR EMBL; U07762; AAC43282.1; -; Genomic_DNA.
DR EMBL; U07748; AAC43269.1; -; Genomic_DNA.
DR EMBL; U07749; AAC43270.1; -; Genomic_DNA.
DR PIR; A30251; AGEC1.
DR RefSeq; NP_416326.1; NC_000913.3.
DR RefSeq; WP_000854958.1; NZ_CP064683.1.
DR PDB; 1K0E; X-ray; 2.00 A; A/B=1-453.
DR PDB; 1K0G; X-ray; 2.05 A; A/B=1-453.
DR PDBsum; 1K0E; -.
DR PDBsum; 1K0G; -.
DR AlphaFoldDB; P05041; -.
DR SMR; P05041; -.
DR BioGRID; 4260345; 170.
DR BioGRID; 850694; 1.
DR ComplexPortal; CPX-5245; Aminodeoxychorismate synthase complex.
DR DIP; DIP-10434N; -.
DR IntAct; P05041; 6.
DR STRING; 511145.b1812; -.
DR DrugBank; DB01942; Formic acid.
DR jPOST; P05041; -.
DR PaxDb; P05041; -.
DR PRIDE; P05041; -.
DR EnsemblBacteria; AAC74882; AAC74882; b1812.
DR EnsemblBacteria; BAA15619; BAA15619; BAA15619.
DR GeneID; 946337; -.
DR KEGG; ecj:JW1801; -.
DR KEGG; eco:b1812; -.
DR PATRIC; fig|511145.12.peg.1889; -.
DR EchoBASE; EB0677; -.
DR eggNOG; COG0147; Bacteria.
DR HOGENOM; CLU_006493_7_2_6; -.
DR InParanoid; P05041; -.
DR PhylomeDB; P05041; -.
DR BioCyc; EcoCyc:PABASYN-COMPI-MON; -.
DR BioCyc; MetaCyc:PABASYN-COMPI-MON; -.
DR BRENDA; 2.6.1.85; 2026.
DR SABIO-RK; P05041; -.
DR UniPathway; UPA00077; UER00149.
DR EvolutionaryTrace; P05041; -.
DR PRO; PR:P05041; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0009356; C:aminodeoxychorismate synthase complex; IPI:ComplexPortal.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0046820; F:4-amino-4-deoxychorismate synthase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0046656; P:folic acid biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0008153; P:para-aminobenzoic acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0046654; P:tetrahydrofolate biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.60.120.10; -; 1.
DR InterPro; IPR005802; ADC_synth_comp_1.
DR InterPro; IPR005801; ADC_synthase.
DR InterPro; IPR019999; Anth_synth_I-like.
DR InterPro; IPR006805; Anth_synth_I_N.
DR InterPro; IPR015890; Chorismate_C.
DR PANTHER; PTHR11236; PTHR11236; 1.
DR Pfam; PF04715; Anth_synt_I_N; 1.
DR Pfam; PF00425; Chorismate_bind; 1.
DR PRINTS; PR00095; ANTSNTHASEI.
DR SUPFAM; SSF56322; SSF56322; 1.
DR TIGRFAMs; TIGR00553; pabB; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Folate biosynthesis; Magnesium;
KW Reference proteome; Transferase.
FT CHAIN 1..453
FT /note="Aminodeoxychorismate synthase component 1"
FT /id="PRO_0000154136"
FT ACT_SITE 258
FT /note="Proton donor"
FT ACT_SITE 274
FT /note="N6-(4-deoxychorismate)-lysine intermediate"
FT BINDING 36
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT /evidence="ECO:0000269|PubMed:11841211"
FT BINDING 43..46
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT BINDING 240..242
FT /ligand="L-tryptophan"
FT /ligand_id="ChEBI:CHEBI:57912"
FT MUTAGEN 258
FT /note="E->A: The reaction is extremely slow."
FT /evidence="ECO:0000269|PubMed:16605270"
FT MUTAGEN 258
FT /note="E->D: The reaction is extremely slow."
FT /evidence="ECO:0000269|PubMed:16605270"
FT MUTAGEN 274
FT /note="K->A: Absence of covalent intermediate. Addition of
FT ammonia allows the formation of the covalent intermediate
FT and shows that ammonia can replace the function of K-274.
FT Reduced catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:14982443,
FT ECO:0000269|PubMed:16605270"
FT MUTAGEN 274
FT /note="K->R: Absence of covalent intermediate."
FT /evidence="ECO:0000269|PubMed:14982443,
FT ECO:0000269|PubMed:16605270"
FT MUTAGEN 274
FT /note="K->R: Reduced catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:14982443,
FT ECO:0000269|PubMed:16605270"
FT MUTAGEN 275
FT /note="G->S: Catalytically inactive for both the glutamine-
FT dependent and ammonia-dependent reactions and fails to
FT interact with PabA."
FT /evidence="ECO:0000269|PubMed:8679677"
FT MUTAGEN 311
FT /note="R->K: Catalytically active in the NH3-dependent, but
FT inactive for the glutamine-dependent reactions and fails to
FT complex with PabA."
FT /evidence="ECO:0000269|PubMed:8679677"
FT MUTAGEN 316
FT /note="R->H: Catalytically inactive for both the glutamine-
FT dependent and ammonia-dependent reactions and fails to
FT interact with PabA."
FT /evidence="ECO:0000269|PubMed:8679677"
FT MUTAGEN 322
FT /note="S->T: Complete loss of aminodeoxychorismate synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:8679677"
FT MUTAGEN 339
FT /note="H->W: Catalytically inactive for both the glutamine-
FT dependent and ammonia-dependent reactions and fails to
FT interact with PabA."
FT /evidence="ECO:0000269|PubMed:8679677"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 17..22
FT /evidence="ECO:0007829|PDB:1K0E"
FT TURN 23..27
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:1K0G"
FT STRAND 46..50
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 54..60
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 79..89
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 133..146
FT /evidence="ECO:0007829|PDB:1K0E"
FT TURN 147..150
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 151..158
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 160..169
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 190..205
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 212..224
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 226..237
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 267..270
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 273..278
FT /evidence="ECO:0007829|PDB:1K0E"
FT TURN 297..301
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 302..314
FT /evidence="ECO:0007829|PDB:1K0E"
FT TURN 315..317
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 324..333
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 335..347
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 354..361
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 365..367
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 369..371
FT /evidence="ECO:0007829|PDB:1K0G"
FT HELIX 372..382
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:1K0E"
FT TURN 388..391
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 392..398
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 403..406
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 410..415
FT /evidence="ECO:0007829|PDB:1K0E"
FT STRAND 418..427
FT /evidence="ECO:0007829|PDB:1K0E"
FT HELIX 433..451
FT /evidence="ECO:0007829|PDB:1K0E"
SQ SEQUENCE 453 AA; 50970 MW; DBF17DD5E17289D8 CRC64;
MKTLSPAVIT LLWRQDAAEF YFSRLSHLPW AMLLHSGYAD HPYSRFDIVV AEPICTLTTF
GKETVVSESE KRTTTTDDPL QVLQQVLDRA DIRPTHNEDL PFQGGALGLF GYDLGRRFES
LPEIAEQDIV LPDMAVGIYD WALIVDHQRH TVSLLSHNDV NARRAWLESQ QFSPQEDFTL
TSDWQSNMTR EQYGEKFRQV QEYLHSGDCY QVNLAQRFHA TYSGDEWQAF LQLNQANRAP
FSAFLRLEQG AILSLSPERF ILCDNSEIQT RPIKGTLPRL PDPQEDSKQA VKLANSAKDR
AENLMIVDLM RNDIGRVAVA GSVKVPELFV VEPFPAVHHL VSTITAQLPE QLHASDLLRA
AFPGGSITGA PKVRAMEIID ELEPQRRNAW CGSIGYLSFC GNMDTSITIR TLTAINGQIF
CSAGGGIVAD SQEEAEYQET FDKVNRILKQ LEK
