EzCatDB: T00093

DB codeT00093
CATH domainDomain 13.40.190.10Catalytic domain
Domain 23.40.190.10
Domain 33.30.160.40Catalytic domain
E.C.2.5.1.61
CSA2ypn
MACiEM0260


Enzyme Name
Swiss-protKEGG

P06983
Protein namePorphobilinogen deaminasehydroxymethylbilane 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)
SynonymsPBG
EC 2.5.1.61
Hydroxymethylbilane synthase
HMBS
Pre-uroporphyrinogen synthase

KEGG pathways
MAP codePathways
MAP00860Porphyrin and chlorophyll metabolism

Swiss-prot:Accession NumberP06983
Entry nameHEM3_ECOLI
Activity4 porphobilinogen + H(2)O = hydroxymethylbilane + 4 NH(3).
SubunitMonomer.
Subcellular location
CofactorBinds 1 dipyrromethane group covalently.


CofactorsSubstratesProducts
KEGG-idL00012C00931C00001C01024C00014
CompoundDipyrromethane cofactorPorphobilinogenH2OHydroxymethylbilaneNH3
Typearomatic ring (with nitrogen atoms),carboxyl groupamine group,aromatic ring (with nitrogen atoms),carboxyl groupH2Oaromatic ring (with nitrogen atoms),carbohydrate,carboxyl groupamine group,organic ion
1ah5A01UnboundUnbound
UnboundUnbound
1pdaA01UnboundUnbound
UnboundUnbound
1ypnA01UnboundUnbound
UnboundUnbound
2ypnA01UnboundUnbound
UnboundUnbound
1gtkA01UnboundUnbound
UnboundUnbound
1ah5A02UnboundUnbound
UnboundUnbound
1pdaA02UnboundUnbound
UnboundUnbound
1ypnA02UnboundUnbound
UnboundUnbound
2ypnA02UnboundUnbound
UnboundUnbound
1gtkA02UnboundUnbound
UnboundUnbound
1ah5A03Bound:DPMUnbound
UnboundUnbound
1pdaA03Bound:DPMUnbound
UnboundUnbound
1ypnA03Bound:DPMUnbound
UnboundUnbound
2ypnA03Bound:DPMUnbound
UnboundUnbound
1gtkA03Bound:DPMUnbound
UnboundUnbound

Active-site residues
resource
literature [16], [17], [18], [19]
pdbCatalytic residuesCofactor-binding residues
1ah5A01ASP 84

1pdaA01ASP 84

1ypnA01ASP 84

2ypnA01ASP 84

1gtkA01ASP 84

1ah5A02

1pdaA02

1ypnA02

2ypnA02

1gtkA02

1ah5A03
CYS 242(Dipyrromethane binding)
1pdaA03
CYS 242(Dipyrromethane binding)
1ypnA03
CYS 242(Dipyrromethane binding)
2ypnA03
CYS 242(Dipyrromethane binding)
1gtkA03
CYS 242(Dipyrromethane binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[2]Scheme II, p.911-912
[5]Scheme 2
[7]Scheme II, p.7989-79903
[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.99-1045
[19]Scheme 4, p.189-1923
[20]Fig.2, p.72-73
[24]p.639-640
[25]


references
[1]
PubMed ID3460492
JournalAnn N Y Acad Sci
Year1986
Volume471
Pages138-54
AuthorsBattersby AR
TitleBiosynthesis of the pigments of life.
[2]
PubMed ID3486002
JournalBiochemistry
Year1986
Volume25
Pages905-12
AuthorsEvans JN, Burton G, Fagerness PE, Mackenzie NE, Scott AI
TitleBiosynthesis of porphyrins and corrins. 2. Isolation, purification, and NMR investigations of the porphobilinogen-deaminase covalent complex.
[3]
PubMed ID3486001
JournalBiochemistry
Year1986
Volume25
Pages896-904
AuthorsEvans JN, Davies RC, Boyd AS, Ichinose I, Mackenzie NE, Scott AI, Baxter RL
TitleBiosynthesis of porphyrins and corrins. 1. 1H and 13C NMR spectra of (hydroxymethyl)bilane and uroporphyrinogens I and III.
[4]
PubMed ID3079571
JournalFEBS Lett
Year1987
Volume225
Pages87-92
AuthorsJordan PM, Warren MJ
TitleEvidence for a dipyrromethane cofactor at the catalytic site of E. coli porphobilinogen deaminase.
[5]
PubMed ID3421931
JournalBiochem J
Year1988
Volume252
Pages909-12
AuthorsHart GJ, Miller AD, Battersby AR
TitleEvidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound through the sulphur atom of a cysteine residue.
[6]
PubMed ID3262369
JournalBiochemistry
Year1988
Volume27
Pages4871-9
AuthorsRose S, Frydman RB, de los Santos C, Sburlati A, Valasinas A, Frydman B
TitleSpectroscopic evidence for a porphobilinogen deaminase-tetrapyrrole complex that is an intermediate in the biosynthesis of uroporphyrinogen III.
[7]
PubMed ID3069124
JournalBiochemistry
Year1988
Volume27
Pages7984-90
AuthorsScott AI, Roessner CA, Stolowich NJ, Karuso P, Williams HJ, Grant SK, Gonzalez MD, Hoshino T
TitleSite-directed mutagenesis and high-resolution NMR spectroscopy of the active site of porphobilinogen deaminase.
[8]
PubMed ID3069132
JournalBiochemistry
Year1988
Volume27
Pages9020-30
AuthorsWarren MJ, Jordan PM
TitleInvestigation into the nature of substrate binding to the dipyrromethane cofactor of Escherichia coli porphobilinogen deaminase.
[9]
PubMed ID3042456
JournalFEBS Lett
Year1988
Volume235
Pages189-93
AuthorsJordan PM, Warren MJ, Williams HJ, Stolowich NJ, Roessner CA, Grant SK, Scott AI
TitleIdentification of a cysteine residue as the binding site for the dipyrromethane cofactor at the active site of Escherichia coli porphobilinogen deaminase.
[10]
PubMed ID2644132
JournalFEBS Lett
Year1989
Volume242
Pages319-24
AuthorsScott AI, Clemens KR, Stolowich NJ, Santander PJ, Gonzalez MD, Roessner CA
TitleReconstitution of apo-porphobilinogen deaminase: structural changes induced by cofactor binding.
[11]
CommentsMUTAGENESIS OF ARGININE RESIDUES.
Medline ID92082485
PubMed ID1747120
JournalBiochem J
Year1991
Volume280
Pages445-9
AuthorsJordan PM, Woodcock SC
TitleMutagenesis of arginine residues in the catalytic cleft of Escherichia coli porphobilinogen deaminase that affects dipyrromethane cofactor assembly and tetrapyrrole chain initiation and elongation.
Related Swiss-protP06983
[12]
CommentsMUTAGENESIS OF ARGININE RESIDUES.
Medline ID91222140
PubMed ID2025226
JournalBiochem J
Year1991
Volume275
Pages447-52
AuthorsLander M, Pitt AR, Alefounder PR, Bardy D, Abell C, Battersby AR
TitleStudies on the mechanism of hydroxymethylbilane synthase concerning the role of arginine residues in substrate binding.
Related Swiss-protP06983
[13]
PubMed ID1548705
JournalJ Mol Biol
Year1992
Volume224
Pages269-71
AuthorsJordan PM, Warren MJ, Mgbeje BI, Wood SP, Cooper JB, Louie G, Brownlie P, Lambert R, Blundell TL
TitleCrystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID92396207
PubMed ID1522882
JournalNature
Year1992
Volume359
Pages33-9
AuthorsLouie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Warren MJ, Woodcock SC, Jordan PM
TitleStructure of porphobilinogen deaminase reveals a flexible multidomain polymerase with a single catalytic site.
Related PDB1pda
Related Swiss-protP06983
[15]
PubMed ID8436121
JournalEur J Biochem
Year1993
Volume211
Pages615-24
AuthorsHadener A, Matzinger PK, Malashkevich VN, Louie GV, Wood SP, Oliver P, Alefounder PR, Pitt AR, Abell C, Battersby AR
TitlePurification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli.
[16]
PubMed ID8117733
JournalBiochemistry
Year1994
Volume33
Pages2688-95
AuthorsWoodcock SC, Jordan PM
TitleEvidence 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.
[17]
PubMed ID7842863
JournalCiba Found Symp
Year1994
Volume180
Pages70-89; discussion 89-96
AuthorsJordan PM
TitleThe biosynthesis of uroporphyrinogen III: mechanism of action of porphobilinogen deaminase.
[18]
PubMed ID7842864
JournalCiba Found Symp
Year1994
Volume180
Pages97-104; discussion 105-10
AuthorsLambert R, Brownlie PD, Woodcock SC, Louie GV, Cooper JC, Warren MJ, Jordan PM, Blundell TL, Wood SP
TitleStructural studies on porphobilinogen deaminase.
[19]
PubMed ID7592565
JournalJ Bioenerg Biomembr
Year1995
Volume27
Pages181-95
AuthorsShoolingin-Jordan PM
TitlePorphobilinogen deaminase and uroporphyrinogen III synthase: structure, molecular biology, and mechanism.
[20]
PubMed ID8727319
JournalProteins
Year1996
Volume25
Pages48-78
AuthorsLouie GV, Brownlie PD, Lambert R, Cooper JB, Blundell TL, Wood SP, Malashkevich VN, Hadener A, Warren MJ, Shoolingin-Jordan PM
TitleThe three-dimensional structure of Escherichia coli porphobilinogen deaminase at 1.76-A resolution.
[21]
PubMed ID8687374
JournalBiochem J
Year1996
Volume316
Pages373-6
AuthorsShoolingin-Jordan PM, Warren MJ, Awan SJ
TitleDiscovery that the assembly of the dipyrromethane cofactor of porphobilinogen deaminase holoenzyme proceeds initially by the reaction of preuroporphyrinogen with the apoenzyme.
[22]
PubMed ID9230062
JournalBiochemistry
Year1997
Volume36
Pages9273-82
AuthorsAwan SJ, Siligardi G, Shoolingin-Jordan PM, Warren MJ
TitleReconstitution of the holoenzyme form of Escherichia coli porphobilinogen deaminase from apoenzyme with porphobilinogen and preuroporphyrinogen: a study using circular dichroism spectroscopy.
[23]
CommentsX-ray crystallography
JournalJ Chem Soc Faraday Trans
Year1998
Volume94
Pages2615-22
AuthorsHelliwell JR, Nieh YP, Raftery J, Cassetta A, Habash J, Carr PD, Ursby T, Wulff M, Thompson AW, Niemann AC, Hadener A
TitleTime-resolved structures of hydroxymethylbilane synthase (Lys59Gln mutant) as it is loaded with substrate in the crystal determined by Laue diffraction.
Related PDB1ypn
[24]
CommentsX-ray crystallography
PubMed ID10089459
JournalActa Crystallogr D Biol Crystallogr
Year1999
Volume55
Pages631-43
AuthorsHadener 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
TitleDetermination of the structure of seleno-methionine-labelled hydroxymethylbilane synthase in its active form by multi-wavelength anomalous dispersion.
Related PDB1ah5,2ypn
[25]
PubMed ID12555854
JournalFaraday Discuss
Year2003
Volume122
Pages131-44
AuthorsHelliwell JR, Nieh YP, Habash J, Faulder PF, Raftery J, Cianci M, Wulff M, Hadener A
TitleTime-resolved and static-ensemble structural chemistry of hydroxymethylbilane synthase.

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.

createdupdated
2004-04-162009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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