DB code: T00093

CATH domain 3.40.190.10 : D-Maltodextrin-Binding Protein; domain 2 Catalytic domain
3.40.190.10 : D-Maltodextrin-Binding Protein; domain 2
3.30.160.40 : Double Stranded RNA Binding Domain Catalytic domain
E.C. 2.5.1.61
CSA 2ypn
M-CSA 2ypn
MACiE M0260

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P06983 Porphobilinogen deaminase
PBG
EC 2.5.1.61
Hydroxymethylbilane synthase
HMBS
Pre-uroporphyrinogen synthase
YP_026260.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_491637.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF01379 (Porphobil_deam)
PF03900 (Porphobil_deamC)
[Graphical View]

KEGG enzyme name
hydroxymethylbilane synthase
HMB-synthase
porphobilinogen deaminase
pre-uroporphyrinogen synthase
uroporphyrinogen I synthase
uroporphyrinogen I synthetase
uroporphyrinogen synthase
uroporphyrinogen synthetase
porphobilinogen ammonia-lyase (polymerizing)
(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase(hydrolysing)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P06983 HEM3_ECOLI 4 porphobilinogen + H(2)O = hydroxymethylbilane + 4 NH(3). Monomer. Binds 1 dipyrromethane group covalently.

KEGG Pathways
Map code Pathways E.C.
MAP00860 Porphyrin and chlorophyll metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id L00012 C00931 C00001 C01024 C00014
E.C.
Compound Dipyrromethane cofactor Porphobilinogen H2O Hydroxymethylbilane NH3
Type aromatic ring (with nitrogen atoms),carboxyl group amine group,aromatic ring (with nitrogen atoms),carboxyl group H2O aromatic ring (with nitrogen atoms),carbohydrate,carboxyl group amine group,organic ion
ChEBI 42121
17381
15377
16645
16134
PubChem 5460481
1021
22247451
962
788
222
1ah5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1pdaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ypnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
2ypnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1gtkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ah5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1pdaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ypnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
2ypnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1gtkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound
1ah5A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:DPM Unbound Unbound Unbound
1pdaA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:DPM Unbound Unbound Unbound
1ypnA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:DPM Unbound Unbound Unbound
2ypnA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:DPM Unbound Unbound Unbound
1gtkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:DPM Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [16], [17], [18], [19]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ah5A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 84
1pdaA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 84
1ypnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 84
2ypnA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 84
1gtkA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 84
1ah5A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1pdaA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ypnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2ypnA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1gtkA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ah5A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 242(Dipyrromethane binding)
1pdaA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 242(Dipyrromethane binding)
1ypnA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 242(Dipyrromethane binding)
2ypnA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 242(Dipyrromethane binding)
1gtkA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 242(Dipyrromethane binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[2]
Scheme II, p.911-912
[5]
Scheme 2
[7]
Scheme II, p.7989-7990 3
[8]
Scheme IV, p.9028-9029
[10]
Fig.5, p.324
[14]
Fig.1, p.33, p.38-39
[16]
Scheme 2, Scheme 3, p.2693-2694
[17]
Fig.6, Fig.7, Fig.8, p.81-84
[18]
Fig.3, p.99-104 5
[19]
Scheme 4, p.189-192 3
[20]
Fig.2, p.72-73
[24]
p.639-640
[25]

References
[1]
Resource
Comments
Medline ID
PubMed ID 3460492
Journal Ann N Y Acad Sci
Year 1986
Volume 471
Pages 138-54
Authors Battersby AR
Title Biosynthesis of the pigments of life.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3486002
Journal Biochemistry
Year 1986
Volume 25
Pages 905-12
Authors Evans JN, Burton G, Fagerness PE, Mackenzie NE, Scott AI
Title Biosynthesis of porphyrins and corrins. 2. Isolation, purification, and NMR investigations of the porphobilinogen-deaminase covalent complex.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 3486001
Journal Biochemistry
Year 1986
Volume 25
Pages 896-904
Authors Evans JN, Davies RC, Boyd AS, Ichinose I, Mackenzie NE, Scott AI, Baxter RL
Title Biosynthesis of porphyrins and corrins. 1. 1H and 13C NMR spectra of (hydroxymethyl)bilane and uroporphyrinogens I and III.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 3079571
Journal FEBS Lett
Year 1987
Volume 225
Pages 87-92
Authors Jordan PM, Warren MJ
Title Evidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 3421931
Journal Biochem J
Year 1988
Volume 252
Pages 909-12
Authors Hart GJ, Miller AD, Battersby AR
Title Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound through the sulphur atom of a cysteine residue.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 3262369
Journal Biochemistry
Year 1988
Volume 27
Pages 4871-9
Authors Rose S, Frydman RB, de los Santos C, Sburlati A, Valasinas A, Frydman B
Title Spectroscopic evidence for a porphobilinogen deaminase-tetrapyrrole complex that is an intermediate in the biosynthesis of uroporphyrinogen III.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 3069124
Journal Biochemistry
Year 1988
Volume 27
Pages 7984-90
Authors Scott AI, Roessner CA, Stolowich NJ, Karuso P, Williams HJ, Grant SK, Gonzalez MD, Hoshino T
Title Site-directed mutagenesis and high-resolution NMR spectroscopy of the active site of porphobilinogen deaminase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 3069132
Journal Biochemistry
Year 1988
Volume 27
Pages 9020-30
Authors Warren MJ, Jordan PM
Title Investigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase.
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 3042456
Journal FEBS Lett
Year 1988
Volume 235
Pages 189-93
Authors Jordan PM, Warren MJ, Williams HJ, Stolowich NJ, Roessner CA, Grant SK, Scott AI
Title Identification of a cysteine residue as the binding site for the dipyrromethane cofactor at the active site of Escherichia coli porphobilinogen deaminase.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 2644132
Journal FEBS Lett
Year 1989
Volume 242
Pages 319-24
Authors Scott AI, Clemens KR, Stolowich NJ, Santander PJ, Gonzalez MD, Roessner CA
Title Reconstitution of apo-porphobilinogen deaminase: structural changes induced by cofactor binding.
Related PDB
Related UniProtKB
[11]
Resource
Comments MUTAGENESIS OF ARGININE RESIDUES.
Medline ID 92082485
PubMed ID 1747120
Journal Biochem J
Year 1991
Volume 280
Pages 445-9
Authors Jordan PM, Woodcock SC
Title Mutagenesis of arginine residues in the catalytic cleft of Escherichia coli porphobilinogen deaminase that affects dipyrromethane cofactor assembly and tetrapyrrole chain initiation and elongation.
Related PDB
Related UniProtKB P06983
[12]
Resource
Comments MUTAGENESIS OF ARGININE RESIDUES.
Medline ID 91222140
PubMed ID 2025226
Journal Biochem J
Year 1991
Volume 275
Pages 447-52
Authors Lander M, Pitt AR, Alefounder PR, Bardy D, Abell C, Battersby AR
Title Studies on the mechanism of hydroxymethylbilane synthase concerning the role of arginine residues in substrate binding.
Related PDB
Related UniProtKB P06983
[13]
Resource
Comments
Medline ID
PubMed ID 1548705
Journal J Mol Biol
Year 1992
Volume 224
Pages 269-71
Authors Jordan PM, Warren MJ, Mgbeje BI, Wood SP, Cooper JB, Louie G, Brownlie P, Lambert R, Blundell TL
Title Crystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID 92396207
PubMed ID 1522882
Journal Nature
Year 1992
Volume 359
Pages 33-9
Authors Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM
Title Structure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
Related PDB 1pda
Related UniProtKB P06983
[15]
Resource
Comments
Medline ID
PubMed ID 8436121
Journal Eur J Biochem
Year 1993
Volume 211
Pages 615-24
Authors Hadener A, Matzinger PK, Malashkevich VN, Louie GV, Wood SP, Oliver P, Alefounder PR, Pitt AR, Abell C, Battersby AR
Title Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli.
Related PDB
Related UniProtKB
[16]
Resource
Comments
Medline ID
PubMed ID 8117733
Journal Biochemistry
Year 1994
Volume 33
Pages 2688-95
Authors Woodcock SC, Jordan PM
Title Evidence for participation of aspartate-84 as a catalytic group at the active site of porphobilinogen deaminase obtained by site-directed mutagenesis of the hemC gene from Escherichia coli.
Related PDB
Related UniProtKB
[17]
Resource
Comments
Medline ID
PubMed ID 7842863
Journal Ciba Found Symp
Year 1994
Volume 180
Pages 70-89; discussion 89-96
Authors Jordan PM
Title The biosynthesis of uroporphyrinogen III: mechanism of action of porphobilinogen deaminase.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 7842864
Journal Ciba Found Symp
Year 1994
Volume 180
Pages 97-104; discussion 105-10
Authors Lambert R, Brownlie PD, Woodcock SC, Louie GV, Cooper JC, Warren MJ, Jordan PM, Blundell TL, Wood SP
Title Structural studies on porphobilinogen deaminase.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 7592565
Journal J Bioenerg Biomembr
Year 1995
Volume 27
Pages 181-95
Authors Shoolingin-Jordan PM
Title Porphobilinogen deaminase and uroporphyrinogen III synthase: structure, molecular biology, and mechanism.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 8727319
Journal Proteins
Year 1996
Volume 25
Pages 48-78
Authors Louie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Malashkevich VN, Hadener A, Warren MJ, Shoolingin-Jordan PM
Title The three-dimensional structure of Escherichia coli porphobilinogen deaminase at 1.76-A resolution.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 8687374
Journal Biochem J
Year 1996
Volume 316
Pages 373-6
Authors Shoolingin-Jordan PM, Warren MJ, Awan SJ
Title Discovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 9230062
Journal Biochemistry
Year 1997
Volume 36
Pages 9273-82
Authors Awan SJ, Siligardi G, Shoolingin-Jordan PM, Warren MJ
Title Reconstitution of the holoenzyme form of Escherichia coli porphobilinogen deaminase from apoenzyme with porphobilinogen and preuroporphyrinogen: a study using circular dichroism spectroscopy.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID
Journal J Chem Soc Faraday Trans
Year 1998
Volume 94
Pages 2615-22
Authors Helliwell JR, Nieh YP, Raftery J, Cassetta A, Habash J, Carr PD, Ursby T, Wulff M, Thompson AW, Niemann AC, Hadener A
Title Time-resolved structures of hydroxymethylbilane synthase (Lys59Gln mutant) as it is loaded with substrate in the crystal determined by Laue diffraction.
Related PDB 1ypn
Related UniProtKB
[24]
Resource
Comments X-ray crystallography
Medline ID
PubMed ID 10089459
Journal Acta Crystallogr D Biol Crystallogr
Year 1999
Volume 55
Pages 631-43
Authors Hadener A, Matzinger PK, Battersby AR, McSweeney S, Thompson AW, Hammersley AP, Harrop SJ, Cassetta A, Deacon A, Hunter WN, Nieh YP, Raftery J, Hunter N, Helliwell JR
Title Determination of the structure of seleno-methionine-labelled hydroxymethylbilane synthase in its active form by multi-wavelength anomalous dispersion.
Related PDB 1ah5 2ypn
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12555854
Journal Faraday Discuss
Year 2003
Volume 122
Pages 131-44
Authors Helliwell JR, Nieh YP, Habash J, Faulder PF, Raftery J, Cianci M, Wulff M, Hadener A
Title Time-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase.
Related PDB
Related UniProtKB

Comments
According to the literature [14], [16], [18], [19] and [20], this enzyme catalyzes the following reactions:
(A) Eliminative double-bond formation at methylene group of the 1st porphobilinogen, releasing ammonia:
(B) Addition of the cofactor, dipyrromethane, to the double-bond:
(C) Eliminative double-bond formation at methylene group of the 2nd porphobilinogen, releasing ammonia:
(D) Addition of the 1st porphobilinogen to the double-bond:
(E) Eliminative double-bond formation at methylene group of the 3rd porphobilinogen, releasing ammonia:
(F) Addition of the 2nd porphobilinogen to the double-bond:
(G) Eliminative double-bond formation at methylene group of the 4th porphobilinogen, releasing ammonia:
(H) Addition of the 3rd porphobilinogen to the double-bond:
(I) Eliminative double-bond formation; Elimination of tetrapyrrole from the cofactor, leading to double-bond formation:
(J) Addition of water to double-bond (hydration):
The reactions, (A), (C), (E) and (G) must be essentially the same, and those, (B), (D), (F), and (H), must be also the same.

Created Updated
2004-04-16 2009-02-26