Q59643 (HEM2_PSEAE) 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
Ordered Locus Names:	PA5243

Organism

Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)

Taxonomic identifier

208964 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Pseudomonadales › Pseudomonadaceae › Pseudomonas

Protein attributes

Sequence length	337 AA.
Sequence status	Complete.
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 By similarity.
Catalytic activity	2 5-aminolevulinate = porphobilinogen + 2 H2O. Ref.5
Enzyme regulation	Stimulated by magnesium ions.
Pathway	Porphyrin metabolism; protoporphyrin-IX biosynthesis; coproporphyrinogen-III from 5-aminolevulinate: step 1/4.
Subunit structure	Homooctamer; formed by oligomerization of dimers. Ref.3
Sequence similarities	Belongs to the ALADH family.

Ontologies

Keywords
Biological process	Heme biosynthesis Porphyrin biosynthesis
Ligand	Magnesium Metal-binding
Molecular function	Lyase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	heme biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW porphobilinogen synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 337

337

Delta-aminolevulinic acid dehydratase

PRO_0000140507

Sites

Active site

205

1

Schiff-base intermediate with substrate Ref.4 Ref.5

Active site

260

1

Schiff-base intermediate with substrate Ref.4 Ref.5

Metal binding

245

1

Magnesium

Binding site

215

1

Substrate 1

Binding site

229

1

Substrate 1

Binding site

286

1

Substrate 2

Binding site

324

1

Substrate 2

Secondary structure

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337

Helix Strand Turn

Details...

Turn

10 – 12

3

Turn

15 – 19

5

Helix

22 – 28

7

Helix

35 – 37

3

Beta strand

38 – 49

12

Beta strand

51 – 53

3

Beta strand

61 – 64

4

Helix

65 – 77

13

Beta strand

82 – 87

6

Helix

91 – 93

3

Beta strand

95 – 97

3

Helix

99 – 102

4

Helix

107 – 118

12

Beta strand

122 – 128

7

Turn

131 – 133

3

Helix

150 – 166

17

Beta strand

170 – 174

5

Helix

181 – 191

11

Beta strand

198 – 206

9

Helix

209 – 211

3

Helix

212 – 216

5

Helix

229 – 231

3

Helix

240 – 251

12

Beta strand

255 – 261

7

Helix

263 – 265

3

Helix

266 – 276

11

Beta strand

280 – 284

5

Helix

286 – 297

12

Helix

305 – 316

12

Beta strand

319 – 323

5

Helix

326 – 334

9

Sequences

	Sequence		Length	Mass (Da)
	Q59643 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 7D650C49795D542C	FASTA	337	37,037
	10 20 30 40 50 60 MSFTPANRAY PYTRLRRNRR DDFSRRLVRE NVLTVDDLIL PVFVLDGVNQ RESIPSMPGV 70 80 90 100 110 120 ERLSIDQLLI EAEEWVALGI PALALFPVTP VEKKSLDAAE AYNPEGIAQR ATRALRERFP 130 140 150 160 170 180 ELGIITDVAL DPFTTHGQDG ILDDDGYVLN DVSIDVLVRQ ALSHAEAGAQ VVAPSDMMDG 190 200 210 220 230 240 RIGAIREALE SAGHTNVRIM AYSAKYASAY YGPFRDAVGS ASNLGKGNKA TYQMDPANSD 250 260 270 280 290 300 EALHEVAADL AEGADMVMVK PGMPYLDIVR RVKDEFRAPT FVYQVSGEYA MHMGAIQNGW 310 320 330 LAESVILESL TAFKRAGADG ILTYFAKQAA EQLRRGR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, mapping and functional characterization of the hemB gene of Pseudomonas aeruginosa, which encodes a magnesium-dependent 5-aminolevulinic acid dehydratase." Frankenberg N., Kittel T., Hungerer C., Roemling U., Jahn D. Mol. Gen. Genet. 257:485-489(1998) [PubMed: 9529530] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
[2]	"Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen." Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P., Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M., Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y., Brody L.L., Coulter S.N., Folger K.R. , Kas A., Larbig K., Lim R.M., Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J., Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V. Nature 406:959-964(2000) [PubMed: 10984043] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228.
[3]	"High resolution crystal structure of a Mg(2+)-dependent porphobilinogen synthase." Frankenberg N., Erskine P.T., Cooper J.B., Shoolingin-Jordan P.M., Jahn D., Heinz D.W. J. Mol. Biol. 289:591-602(1999) [PubMed: 10356331] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) IN COMPLEX WITH LEVULINIC ACID AND MAGNESIUM, SUBUNIT.
[4]	"Structure of porphobilinogen synthase from Pseudomonas aeruginosa in complex with 5-fluorolevulinic acid suggests a double Schiff base mechanism." Frere F., Schubert W.-D., Stauffer F., Frankenberg N., Neier R., Jahn D., Heinz D.W. J. Mol. Biol. 320:237-247(2002) [PubMed: 12079382] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF MUTANT ASN-139 IN COMPLEX WITH 5-FLUOROLEVULINIC ACID AND MAGNESIUM, COFACTOR, ACTIVE SITE.
[5]	"Probing the active site of Pseudomonas aeruginosa porphobilinogen synthase using newly developed inhibitors." Frere F., Nentwich M., Gacond S., Heinz D.W., Neier R., Frankenberg-Dinkel N. Biochemistry 45:8243-8253(2006) [PubMed: 16819823] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEXES WITH MAGNESIUM; 5-HYDROXYLEVULINIC ACID AND OTHER INHIBITORS, CATALYTIC ACTIVITY, COFACTOR, ACTIVE SITE.
[6]	"Structure of the heme biosynthetic Pseudomonas aeruginosa porphobilinogen synthase in complex with the antibiotic alaremycin." Heinemann I.U., Schulz C., Schubert W.D., Heinz D.W., Wang Y.G., Kobayashi Y., Awa Y., Wachi M., Jahn D., Jahn M. Antimicrob. Agents Chemother. 54:267-272(2010) [PubMed: 19822707] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH ALAREMYCIN.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X91820 Genomic DNA. Translation: CAA62930.1.
AE004091 Genomic DNA. Translation: AAG08628.1.

PIR

S60577.

RefSeq

NP_253930.1. NC_002516.2.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B4K	X-ray	1.67	A/B	1-337	[»]
1GZG	X-ray	1.66	A/B	1-337	[»]
1W54	X-ray	2.20	A/B	1-337	[»]
1W56	X-ray	1.70	A/B	1-337	[»]
1W5M	X-ray	1.60	A/B	1-337	[»]
1W5N	X-ray	1.65	A/B	1-337	[»]
1W5O	X-ray	1.85	A/B	1-337	[»]
1W5P	X-ray	1.55	A/B	1-337	[»]
1W5Q	X-ray	1.40	A/B	1-337	[»]
2C13	X-ray	2.15	A/B	1-337	[»]
2C14	X-ray	1.90	A/B	1-337	[»]
2C15	X-ray	1.48	A/B	1-337	[»]
2C16	X-ray	2.02	A/B	1-337	[»]
2C18	X-ray	1.93	A/B	1-337	[»]
2C19	X-ray	2.05	A/B	1-337	[»]
2WOQ	X-ray	1.75	A	1-337	[»]

ProteinModelPortal

Q59643.

SMR

Q59643. Positions 10-335.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

879701.

GenomeReviews

Gene locus PA5243 in contig AE004091_GR.

KEGG

pae:PA5243.

PATRIC

19845337. VBIPseAer58763_5495.

Organism-specific databases

PseudoCAP

PA5243.

Phylogenomic databases

HOGENOM

HBG285270.

OMA

FTSHGHD.

ProtClustDB

PRK09283.

Enzyme and pathway databases

BioCyc

PAER208964:PA5243-MONOMER.

Family and domain databases

InterPro

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

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

KO

K01698.

PANTHER

PTHR11458. AlaD_dehydratase. 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...

Entry information

Entry name

HEM2_PSEAE

Accession

Primary (citable) accession number: Q59643

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	January 25, 2012
This is version 90 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program