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 24-JAN-2024, entry version 136. 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; Pseudomonadota; 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 jPOST; P0ACB2; -. DR PaxDb; 511145-b0369; -. DR EnsemblBacteria; AAC73472; AAC73472; b0369. DR GeneID; 83577661; -. 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 OrthoDB; 9805001at2; -. DR PhylomeDB; P0ACB2; -. DR BioCyc; EcoCyc:PORPHOBILSYNTH-MONOMER; -. DR BioCyc; MetaCyc:PORPHOBILSYNTH-MONOMER; -. 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 CDD; cd00384; ALAD_PBGS; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 1. DR InterPro; IPR001731; ALAD. DR InterPro; IPR030656; ALAD_AS. DR InterPro; IPR013785; Aldolase_TIM. DR PANTHER; PTHR11458; DELTA-AMINOLEVULINIC ACID DEHYDRATASE; 1. DR PANTHER; PTHR11458:SF1; DELTA-AMINOLEVULINIC ACID DEHYDRATASE; 1. DR Pfam; PF00490; ALAD; 1. DR PIRSF; PIRSF001415; Porphbilin_synth; 1. DR PRINTS; PR00144; DALDHYDRTASE. DR SMART; SM01004; ALAD; 1. DR SUPFAM; SSF51569; Aldolase; 1. DR PROSITE; PS00169; D_ALA_DEHYDRATASE; 1. DR SWISS-2DPAGE; P0ACB2; -. 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 //