P0ACB2 (HEM2_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta-aminolevulinic acid dehydratase
Short name=ALAD
Short name=ALADH
EC=4.2.1.24

Alternative name(s):
Porphobilinogen synthase

Gene names

Name:	hemB
Synonyms:	ncf
Ordered Locus Names:	b0369, JW0361

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	324 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O.
Cofactor	Binds 1 zinc ion per monomer. Ref.9 Ref.10 Ref.11 Ref.12
Enzyme regulation	Allosteric enzyme. Stimulated by magnesium ions. Ref.9
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer. Ref.10 Ref.11 Ref.12
Sequence similarities	Belongs to the ALADH family.
Sequence caution	The sequence AAB18092.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence BAA12842.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Ligand	Magnesium Metal-binding Zinc
Molecular function	Lyase
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	heme biosynthetic process Inferred from mutant phenotype PubMed 3276659. Source: EcoliWiki protoporphyrinogen IX biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	cytosol Inferred from direct assay PubMed 16858726. Source: UniProtKB
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW porphobilinogen synthase activity Inferred from mutant phenotype PubMed 3276659. Source: EcoliWiki
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 324

323

Delta-aminolevulinic acid dehydratase

PRO_0000140501

Sites

Active site

195

1

Schiff-base intermediate with substrate Ref.11 Ref.12

Active site

247

1

Schiff-base intermediate with substrate Ref.11 Ref.12

Metal binding

120

1

Zinc; catalytic

Metal binding

122

1

Zinc; catalytic

Metal binding

130

1

Zinc; catalytic

Metal binding

232

1

Magnesium

Binding site

205

1

Substrate 1

Binding site

216

1

Substrate 1

Binding site

273

1

Substrate 2

Binding site

312

1

Substrate 2

Experimental info

Mutagenesis

127

1

H → A: No significant effect on activity; when associated with A-129. Ref.9

Mutagenesis

129

1

H → A: No significant effect on activity; when associated with A-127. Ref.9

Sequence conflict

18 – 19

2

RA → PR in AAA62629. Ref.1

Sequence conflict

19 – 42

24

AMFEE…EEEID → VCLKRQHLSLTTWCCRSLLK KKLT in CAA35467. Ref.2

Sequence conflict

90 – 91

2

SD → ER in AAA62629. Ref.1

Sequence conflict

104

1

R → P in AAA62629. Ref.1

Sequence conflict

226

1

R → P in CAA35467. Ref.2

Sequence conflict

227

1

R → A in AAA62629. Ref.1

Sequence conflict

229

1

A → G in AAA62629. Ref.1

Sequence conflict

231

1

R → A in AAA62629. Ref.1

Sequence conflict

233

1

S → Y in AAA62629. Ref.1

Sequence conflict

241

1

A → P in AAA62629. Ref.1

Sequence conflict

254

1

D → N in AAA62629. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

324

Helix Strand Turn

Details...

Helix

8 – 12

5

Helix

15 – 21

7

Helix

28 – 30

3

Beta strand

31 – 38

8

Beta strand

48 – 50

3

Beta strand

54 – 57

4

Helix

58 – 60

3

Helix

61 – 70

10

Beta strand

75 – 81

7

Beta strand

86 – 88

3

Helix

90 – 93

4

Helix

98 – 109

12

Beta strand

113 – 119

7

Turn

122 – 124

3

Beta strand

125 – 127

3

Beta strand

129 – 133

5

Beta strand

135 – 138

4

Helix

140 – 157

18

Beta strand

160 – 164

5

Helix

171 – 181

11

Beta strand

188 – 190

3

Beta strand

194 – 196

3

Helix

199 – 201

3

Helix

202 – 208

7

Turn

217 – 219

3

Helix

226 – 238

13

Beta strand

242 – 248

7

Helix

250 – 252

3

Helix

253 – 260

8

Beta strand

267 – 271

5

Helix

273 – 284

12

Helix

290 – 303

14

Beta strand

307 – 311

5

Helix

314 – 319

6

Sequences

	Sequence		Length	Mass (Da)
	P0ACB2 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: CE814E5705BFD255	FASTA	324	35,625
	10 20 30 40 50 60 MTDLIQRPRR LRKSPALRAM FEETTLSLND LVLPIFVEEE IDDYKAVEAM PGVMRIPEKH 70 80 90 100 110 120 LAREIERIAN AGIRSVMTFG ISHHTDETGS DAWREDGLVA RMSRICKQTV PEMIVMSDTC 130 140 150 160 170 180 FCEYTSHGHC GVLCEHGVDN DATLENLGKQ AVVAAAAGAD FIAPSAAMDG QVQAIRQALD 190 200 210 220 230 240 AAGFKDTAIM SYSTKFASSF YGPFREAAGS ALKGDRKSYQ MNPMNRREAI RESLLDEAQG 250 260 270 280 290 300 ADCLMVKPAG AYLDIVRELR ERTELPIGAY QVSGEYAMIK FAALAGAIDE EKVVLESLGS 310 320 IKRAGADLIF SYFALDLAEK KILR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The structure of the Escherichia coli hemB gene." Li J.-M., Russell C.S., Cosloy S.D. Gene 75:177-184(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"Nucleotide sequence of the hemB gene of Escherichia coli K12." Echelard Y., Dymetryszyn J., Drolet M., Sasarman A. Mol. Gen. Genet. 214:503-508(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[3]	Sigurdsson E., Backman V.M., Eggertsson G. Submitted (AUG-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[4]	Nashimoto H., Saito N. Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[5]	"Sequence of minutes 4-25 of Escherichia coli." Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W. Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[6]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[7]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[8]	"Purification and characterization of 5-aminolaevulinic acid dehydratase from Escherichia coli and a study of the reactive thiols at the metal-binding domain." Spencer P., Jordan P.M. Biochem. J. 290:279-287(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, PROTEIN SEQUENCE OF 2-6; 96-135 AND 238-254.
[9]	"The phylogenetically conserved histidines of Escherichia coli porphobilinogen synthase are not required for catalysis." Mitchell L.W., Volin M., Jaffe E.K. J. Biol. Chem. 270:24054-24059(1995) [PubMed] [Europe PMC] [Abstract] Cited for: COFACTOR, ENZYME REGULATION, MUTAGENESIS OF HIS-127 AND HIS-129.
[10]	"X-ray structure of 5-aminolevulinic acid dehydratase from Escherichia coli complexed with the inhibitor levulinic acid at 2.0-A resolution." Erskine P.T., Norton E., Cooper J.B., Lambert R., Coker A., Lewis G., Spencer P., Sarwar M., Wood S.P., Warren M.J., Shoolingin-Jordan P.M. Biochemistry 38:4266-4276(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH LEVULINIC ACID AND ZINC IONS, SUBUNIT, COFACTOR.
[11]	"Mechanistic basis for suicide inactivation of porphobilinogen synthase by 4,7-dioxosebacic acid, an inhibitor that shows dramatic species selectivity." Kervinen J., Jaffe E.K., Stauffer F., Neier R., Wlodawer A., Zdanov A. Biochemistry 40:8227-8236(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH 4,7-DIOXOSEBACIC ACID; ZINC AND MAGNESIUM, ACTIVE SITE, SUBUNIT, COFACTOR.
[12]	"Species-specific inhibition of porphobilinogen synthase by 4-oxosebacic acid." Jaffe E.K., Kervinen J., Martins J., Stauffer F., Neier R., Wlodawer A., Zdanov A. J. Biol. Chem. 277:19792-19799(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) IN COMPLEX WITH 4-OXOSEBACIC ACID; ZINC AND MAGNESIUM, ACTIVE SITE, SUBUNIT, COFACTOR.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M24488 Genomic DNA. Translation: AAA62629.1.
X17417 Genomic DNA. Translation: CAA35467.1.
L44595 Genomic DNA. Translation: AAB52499.1.
D85613 Genomic DNA. Translation: BAA12842.1. Different initiation.
U73857 Genomic DNA. Translation: AAB18092.1. Different initiation.
U00096 Genomic DNA. Translation: AAC73472.2.
AP009048 Genomic DNA. Translation: BAE76150.1.

PIR

SYECPF. A64765.

RefSeq

NP_414903.4. NC_000913.2.
YP_488662.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B4E	X-ray	2.00	A	2-324	[»]
1I8J	X-ray	1.90	A/B	2-324	[»]
1L6S	X-ray	1.70	A/B	2-324	[»]
1L6Y	X-ray	1.90	A/B	2-324	[»]

ProteinModelPortal

P0ACB2.

SMR

P0ACB2. Positions 2-324.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36209N.

IntAct

P0ACB2. 5 interactions.

STRING

511145.b0369.

2D gel databases

SWISS-2DPAGE

P0ACB2.

Proteomic databases

PaxDb

P0ACB2.

PRIDE

P0ACB2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC73472; AAC73472; b0369.
BAE76150; BAE76150; BAE76150.

GeneID

12932508.
945017.

KEGG

ecj:Y75_p0358.
eco:b0369.

PATRIC

32115877. VBIEscCol129921_0380.

Organism-specific databases

EchoBASE

EB0423.

EcoGene

EG10428. hemB.

Phylogenomic databases

eggNOG

COG0113.

HOGENOM

HOG000020323.

KO

K01698.

OMA

MIISYHA.

ProtClustDB

PRK09283.

Enzyme and pathway databases

BioCyc

EcoCyc:PORPHOBILSYNTH-MONOMER.
ECOL316407:JW0361-MONOMER.
MetaCyc:PORPHOBILSYNTH-MONOMER.

UniPathway

UPA00251; UER00318.

Gene expression databases

Genevestigator

P0ACB2.

Family and domain databases

Gene3D

3.20.20.70. 1 hit.

InterPro

IPR013785. Aldolase_TIM.
IPR001731. Porphobilinogen_synth.
[Graphical view]

PANTHER

PTHR11458. PTHR11458. 1 hit.

Pfam

PF00490. ALAD. 1 hit.
[Graphical view]

PIRSF

PIRSF001415. Porphbilin_synth. 1 hit.

PRINTS

PR00144. DALDHYDRTASE.

SMART

SM01004. ALAD. 1 hit.
[Graphical view]

PROSITE

PS00169. D_ALA_DEHYDRATASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P0ACB2.

EvolutionaryTrace

P0ACB2.

Entry information

Entry name

HEM2_ECOLI

Accession

Primary (citable) accession number: P0ACB2
Secondary accession number(s): P15002, P78247, Q2MC56

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2005
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program