HEM2_ECOLI
ID HEM2_ECOLI Reviewed; 324 AA.
AC P0ACB2; P15002; P78247; Q2MC56;
DT 08-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Delta-aminolevulinic acid dehydratase;
DE Short=ALAD;
DE Short=ALADH;
DE EC=4.2.1.24 {ECO:0000305|PubMed:8439296};
DE AltName: Full=Porphobilinogen synthase;
GN Name=hemB; Synonyms=ncf; OrderedLocusNames=b0369, JW0361;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2656410; DOI=10.1016/0378-1119(89)90394-6;
RA Li J.-M., Russell C.S., Cosloy S.D.;
RT "The structure of the Escherichia coli hemB gene.";
RL Gene 75:177-184(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=2464127; DOI=10.1007/bf00330487;
RA Echelard Y., Dymetryszyn J., Drolet M., Sasarman A.;
RT "Nucleotide sequence of the hemB gene of Escherichia coli K12.";
RL Mol. Gen. Genet. 214:503-508(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Sigurdsson E., Backman V.M., Eggertsson G.;
RL Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RA Nashimoto H., Saito N.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
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 [8]
RP PROTEIN SEQUENCE OF 2-6; 96-135 AND 238-254, COFACTOR, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND SUBUNIT.
RX PubMed=8439296; DOI=10.1042/bj2900279;
RA Spencer P., Jordan P.M.;
RT "Purification and characterization of 5-aminolaevulinic acid dehydratase
RT from Escherichia coli and a study of the reactive thiols at the metal-
RT binding domain.";
RL Biochem. J. 290:279-287(1993).
RN [9]
RP COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-127 AND HIS-129.
RX PubMed=7592604; DOI=10.1074/jbc.270.41.24054;
RA Mitchell L.W., Volin M., Jaffe E.K.;
RT "The phylogenetically conserved histidines of Escherichia coli
RT porphobilinogen synthase are not required for catalysis.";
RL J. Biol. Chem. 270:24054-24059(1995).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH LEVULINIC ACID AND
RP ZINC IONS, SUBUNIT, AND COFACTOR.
RX PubMed=10194344; DOI=10.1021/bi982137w;
RA Erskine P.T., Norton E., Cooper J.B., Lambert R., Coker A., Lewis G.,
RA Spencer P., Sarwar M., Wood S.P., Warren M.J., Shoolingin-Jordan P.M.;
RT "X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli
RT complexed with the inhibitor levulinic acid at 2.0-A resolution.";
RL Biochemistry 38:4266-4276(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH 4,7-DIOXOSEBACIC
RP ACID; ZINC AND MAGNESIUM, ACTIVE SITE, SUBUNIT, AND COFACTOR.
RX PubMed=11444968; DOI=10.1021/bi010656k;
RA Kervinen J., Jaffe E.K., Stauffer F., Neier R., Wlodawer A., Zdanov A.;
RT "Mechanistic basis for suicide inactivation of porphobilinogen synthase by
RT 4,7-dioxosebacic acid, an inhibitor that shows dramatic species
RT selectivity.";
RL Biochemistry 40:8227-8236(2001).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH 4-OXOSEBACIC ACID;
RP ZINC AND MAGNESIUM, ACTIVE SITE, SUBUNIT, AND COFACTOR.
RX PubMed=11909869; DOI=10.1074/jbc.m201486200;
RA Jaffe E.K., Kervinen J., Martins J., Stauffer F., Neier R., Wlodawer A.,
RA Zdanov A.;
RT "Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic
RT acid.";
RL J. Biol. Chem. 277:19792-19799(2002).
CC -!- FUNCTION: Catalyzes an early step in the biosynthesis of tetrapyrroles.
CC Binds two molecules of 5-aminolevulinate per subunit, each at a
CC distinct site, and catalyzes their condensation to form
CC porphobilinogen.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 5-aminolevulinate = H(+) + 2 H2O + porphobilinogen;
CC Xref=Rhea:RHEA:24064, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:58126, ChEBI:CHEBI:356416; EC=4.2.1.24;
CC Evidence={ECO:0000305|PubMed:8439296};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:10194344, ECO:0000269|PubMed:11444968,
CC ECO:0000269|PubMed:11909869, ECO:0000269|PubMed:7592604,
CC ECO:0000269|PubMed:8439296};
CC Note=Binds 1 zinc ion per monomer. {ECO:0000269|PubMed:10194344,
CC ECO:0000269|PubMed:11444968, ECO:0000269|PubMed:11909869,
CC ECO:0000269|PubMed:7592604};
CC -!- ACTIVITY REGULATION: Allosteric enzyme. Stimulated by magnesium ions.
CC {ECO:0000269|PubMed:7592604}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=800 uM for 5-aminolevulinic acid {ECO:0000269|PubMed:8439296};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:8439296};
CC -!- PATHWAY: Porphyrin-containing compound metabolism; protoporphyrin-IX
CC biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
CC -!- SUBUNIT: Homooctamer. {ECO:0000269|PubMed:10194344,
CC ECO:0000269|PubMed:11444968, ECO:0000269|PubMed:11909869,
CC ECO:0000269|PubMed:8439296}.
CC -!- SIMILARITY: Belongs to the ALAD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB18092.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA12842.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M24488; AAA62629.1; -; Genomic_DNA.
DR EMBL; X17417; CAA35467.1; -; Genomic_DNA.
DR EMBL; L44595; AAB52499.1; -; Genomic_DNA.
DR EMBL; D85613; BAA12842.1; ALT_INIT; Genomic_DNA.
DR EMBL; U73857; AAB18092.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC73472.2; -; Genomic_DNA.
DR EMBL; AP009048; BAE76150.1; -; Genomic_DNA.
DR PIR; A64765; SYECPF.
DR RefSeq; NP_414903.4; NC_000913.3.
DR RefSeq; WP_001295337.1; NZ_STEB01000036.1.
DR PDB; 1B4E; X-ray; 2.00 A; A=2-324.
DR PDB; 1I8J; X-ray; 1.90 A; A/B=2-324.
DR PDB; 1L6S; X-ray; 1.70 A; A/B=2-324.
DR PDB; 1L6Y; X-ray; 1.90 A; A/B=2-324.
DR PDB; 5MHB; X-ray; 2.10 A; A=1-324.
DR PDBsum; 1B4E; -.
DR PDBsum; 1I8J; -.
DR PDBsum; 1L6S; -.
DR PDBsum; 1L6Y; -.
DR PDBsum; 5MHB; -.
DR AlphaFoldDB; P0ACB2; -.
DR SMR; P0ACB2; -.
DR BioGRID; 4261502; 26.
DR DIP; DIP-36209N; -.
DR IntAct; P0ACB2; 8.
DR MINT; P0ACB2; -.
DR STRING; 511145.b0369; -.
DR BindingDB; P0ACB2; -.
DR ChEMBL; CHEMBL3286083; -.
DR DrugBank; DB04560; 4,7-Dioxosebacic Acid.
DR DrugBank; DB02260; 4-Oxosebacic Acid.
DR DrugBank; DB04530; S,S-(2-Hydroxyethyl)Thiocysteine.
DR SWISS-2DPAGE; P0ACB2; -.
DR jPOST; P0ACB2; -.
DR PaxDb; P0ACB2; -.
DR PRIDE; P0ACB2; -.
DR EnsemblBacteria; AAC73472; AAC73472; b0369.
DR EnsemblBacteria; BAE76150; BAE76150; BAE76150.
DR GeneID; 66671329; -.
DR GeneID; 945017; -.
DR KEGG; ecj:JW0361; -.
DR KEGG; eco:b0369; -.
DR PATRIC; fig|1411691.4.peg.1910; -.
DR EchoBASE; EB0423; -.
DR eggNOG; COG0113; Bacteria.
DR HOGENOM; CLU_035731_0_0_6; -.
DR InParanoid; P0ACB2; -.
DR OMA; YMDIIWR; -.
DR PhylomeDB; P0ACB2; -.
DR BioCyc; EcoCyc:PORPHOBILSYNTH-MON; -.
DR BioCyc; MetaCyc:PORPHOBILSYNTH-MON; -.
DR BRENDA; 4.2.1.24; 2026.
DR SABIO-RK; P0ACB2; -.
DR UniPathway; UPA00251; UER00318.
DR EvolutionaryTrace; P0ACB2; -.
DR PRO; PR:P0ACB2; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0004655; F:porphobilinogen synthase activity; IDA:EcoCyc.
DR GO; GO:0008270; F:zinc ion binding; IDA:EcoCyc.
DR GO; GO:0006783; P:heme biosynthetic process; IMP:EcoliWiki.
DR GO; GO:0006782; P:protoporphyrinogen IX biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR001731; ALAD.
DR InterPro; IPR030656; ALAD_AS.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11458; PTHR11458; 1.
DR Pfam; PF00490; ALAD; 1.
DR PIRSF; PIRSF001415; Porphbilin_synth; 1.
DR PRINTS; PR00144; DALDHYDRTASE.
DR SMART; SM01004; ALAD; 1.
DR PROSITE; PS00169; D_ALA_DEHYDRATASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Allosteric enzyme; Direct protein sequencing;
KW Heme biosynthesis; Lyase; Magnesium; Metal-binding; Porphyrin biosynthesis;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:8439296"
FT CHAIN 2..324
FT /note="Delta-aminolevulinic acid dehydratase"
FT /id="PRO_0000140501"
FT ACT_SITE 195
FT /note="Schiff-base intermediate with substrate"
FT ACT_SITE 247
FT /note="Schiff-base intermediate with substrate"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11444968,
FT ECO:0000269|PubMed:11909869"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11444968,
FT ECO:0000269|PubMed:11909869"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11444968,
FT ECO:0000269|PubMed:11909869"
FT BINDING 205
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT BINDING 216
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="1"
FT BINDING 232
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000269|PubMed:11444968,
FT ECO:0000269|PubMed:11909869"
FT BINDING 273
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT BINDING 312
FT /ligand="5-aminolevulinate"
FT /ligand_id="ChEBI:CHEBI:356416"
FT /ligand_label="2"
FT MUTAGEN 127
FT /note="H->A: No significant effect on activity; when
FT associated with A-129."
FT /evidence="ECO:0000269|PubMed:7592604"
FT MUTAGEN 129
FT /note="H->A: No significant effect on activity; when
FT associated with A-127."
FT /evidence="ECO:0000269|PubMed:7592604"
FT CONFLICT 18..19
FT /note="RA -> PR (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 19..42
FT /note="AMFEETTLSLNDLVLPIFVEEEID -> VCLKRQHLSLTTWCCRSLLKKKLT
FT (in Ref. 2; CAA35467)"
FT /evidence="ECO:0000305"
FT CONFLICT 90..91
FT /note="SD -> ER (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="R -> P (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="R -> P (in Ref. 2; CAA35467)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="R -> A (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 229
FT /note="A -> G (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 231
FT /note="R -> A (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 233
FT /note="S -> Y (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="A -> P (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT CONFLICT 254
FT /note="D -> N (in Ref. 1; AAA62629)"
FT /evidence="ECO:0000305"
FT HELIX 8..12
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 15..21
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 31..38
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 48..50
FT /evidence="ECO:0007829|PDB:1L6Y"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 61..70
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 90..93
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 98..109
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:1L6S"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:1L6Y"
FT STRAND 135..138
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 140..157
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 160..164
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 171..181
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 199..201
FT /evidence="ECO:0007829|PDB:1B4E"
FT HELIX 202..208
FT /evidence="ECO:0007829|PDB:1L6S"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 226..238
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 250..252
FT /evidence="ECO:0007829|PDB:1B4E"
FT HELIX 253..260
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 273..284
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 290..303
FT /evidence="ECO:0007829|PDB:1L6S"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:1L6S"
FT HELIX 314..319
FT /evidence="ECO:0007829|PDB:1L6S"
SQ SEQUENCE 324 AA; 35625 MW; CE814E5705BFD255 CRC64;
MTDLIQRPRR LRKSPALRAM FEETTLSLND LVLPIFVEEE IDDYKAVEAM PGVMRIPEKH
LAREIERIAN AGIRSVMTFG ISHHTDETGS DAWREDGLVA RMSRICKQTV PEMIVMSDTC
FCEYTSHGHC GVLCEHGVDN DATLENLGKQ AVVAAAAGAD FIAPSAAMDG QVQAIRQALD
AAGFKDTAIM SYSTKFASSF YGPFREAAGS ALKGDRKSYQ MNPMNRREAI RESLLDEAQG
ADCLMVKPAG AYLDIVRELR ERTELPIGAY QVSGEYAMIK FAALAGAIDE EKVVLESLGS
IKRAGADLIF SYFALDLAEK KILR
