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Information on EC 2.5.1.61 - hydroxymethylbilane synthase and Organism(s) Escherichia coli and UniProt Accession P06983
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2.5.1.61 hydroxymethylbilane synthaseIUBMB Comments
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
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Word Map
- 2.5.1.61
- porphyria
-
intermittent
- heme
- aip
- erythrocyte
-
delta-aminolevulinic
-
5-aminolevulinic
- gapdh
-
erythroid
-
genorm
- urinary
- dehydratase
- protoporphyrin
-
ferrochelatase
-
normfinder
-
housekeeping
- tetrapyrrole
-
bestkeeper
- coproporphyrinogen
-
neurovisceral
-
ywhaz
- protoporphyrinogen
- pyrrole
- variegate
-
photodynamic
-
erythroid-specific
-
half-normal
-
porphyrinogenic
- coproporphyria
- hematin
-
proto
- tarda
- pharmacology
-
beta-2-microglobulin
- hyponatremia
- diagnostics
-
gata-1
- medicine
-
rpl13a
-
lightcycler
-
cutanea
- beta-globin
-
non-erythroid
-
reffinder
The taxonomic range for the selected organisms is: Escherichia coli
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
porphobilinogen deaminase, hmbs, hydroxymethylbilane synthase, pbg-d, uro-s, pbg deaminase, uroporphyrinogen i synthase, human porphobilinogen deaminase, uroporphyrinogen synthase, uroporphyrinogen i synthetase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
porphobilinogen ammonia-lyase (polymerizing)
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-
-
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pre-uroporphyrinogen synthase
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-
-
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synthase, uroporphyrinogen I
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-
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uroporphyrinogen synthase
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3
reaction mechanism with active site residues R11, D84 and R176 that appear to be involved in controlling crucial steps during tetrapyrrole, detailed interaction analysis, overview. The compactness of the overall protein decreases progressively with addition of each pyrrole ring. domains move apart while the cofactor turn region moves towards the second domain, thus creating space for the pyrrole rings added at each stage. Residues of the flexible active site loop play a significant role in its modulation. During this movement, loop residue D50 interacts with R149 and K55 interacts with Q243, E305 and V306 with an occupancy of 41% along the trajectory. Upon removal of hydroxymethylbilane, the structure of the enzyme gradually relaxes to resemble its initial stage structure, indicating its readiness to resume a new catalytic cycle
PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
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-, -
SYSTEMATIC NAME
IUBMB Comments
porphobilinogen:(4-[2-carboxyethyl]-3-[carboxymethyl]pyrrol-2-yl)methyltransferase (hydrolysing)
The enzyme works by stepwise addition of pyrrolylmethyl groups until a hexapyrrole is present at the active centre. The terminal tetrapyrrole is then hydrolysed to yield the product, leaving a cysteine-bound dipyrrole on which assembly continues. In the presence of a second enzyme, EC 4.2.1.75 uroporphyrinogen-III synthase, which is often called cosynthase, the product is cyclized to form uroporphyrinogen-III. If EC 4.2.1.75 is absent, the hydroxymethylbilane cyclizes spontaneously to form uroporphyrinogen I.
CAS REGISTRY NUMBER
COMMENTARY
9036-47-9
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9074-91-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
porphobilinogen
?
-
-
-
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
4 porphobilinogen
uroporphyrinogen III + 4 NH3
-
in the presence of uroporphyrinogen III cosynthase, EC 4.2.1.75
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
porphobilinogen deaminase, an enzyme in the heme biosynthetic pathway, catalyzes the formation of a linear tetrapyrrole product, 1-hydroxymethylbilane, from four units of porphobilinogen
physiological function
porphobilinogen deaminase catalyzes the formation of 1-hydroxymethylbilane, a crucial intermediate in tetrapyrrole biosynthesis, through a step-wise polymerization of four molecules of porphobilinogen, using a unique dipyrromethane cofactor
additional information
additional information
molecular dynamics simulations for determmination of the exit mechanism of hydroxymethylbilane from the enzyme at the end of the catalytic cycle
additional information
-
molecular dynamics simulations for determmination of the exit mechanism of hydroxymethylbilane from the enzyme at the end of the catalytic cycle
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
K55Q/K59Q
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K55Q-K59Q mutant, lower specific activity than the wild-type enzyme
additional information
-
all, six, methionine residues are replaced by SeMet
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Helliwell, J.R.; Nieh, Y.P.; Raftery, J.; Cassata, A.; Habash, J.; Carr, P.D.; Ursby, T.; Wulff, M.; Thompson, A.W.; Niemann, A.C.; Haedener, A.
Time-resolved structures of hydroxymethylbilane synthase (Lys59Gln mutant) as it is loaded with substrate in the crystal determined by Laue diffraction
J. Chem. Soc. Faraday Trans.
94
2615-2622
1998
Escherichia coli
-
Hart, G.J.; Abell, C.; Battersby, A.R.
Purification, N-terminal amino acid sequence and properties of hydroxymethylbilane synthase (porphobilinogen deaminase) from Escherichia coli
Biochem. J.
240
273-276
1986
Escherichia coli
Mazzetti, M.B.; Tomio, J.M.
Purification and some properties of rat liver uroporphyrinogen I synthase
Anal. Asoc. Quim. Argent.
76
207-215
1988
Chlorella regularis, Escherichia coli, Homo sapiens, Rattus norvegicus, Spinacia oleracea
-
Miller, A.D.; Hart, G.J.; Packman, L.C.; Battersby, A.R.
Evidence that the pyrromethane cofactor of hydroxymethylbilane synthase (porphobilinogen deaminase) is bound to the protein through the sulphur atom of cysteine-242
Biochem. J.
254
915-918
1988
Escherichia coli, Escherichia coli TG1
Beifuss, U.; Hart, G.J.; Miller, A.D.; Battersby, A.R.
13C-N.M.R. Studies on the pyrromethane cofactor of hydroxymethylbilane synthase
Tetrahedron Lett.
29
2591-2594
1988
Escherichia coli
-
Sharif, A.; Smith, A.G.; Abell, C.
Isolation and characterisation of cDNA clone for chlorophyll synthesis enzyme from Euglena gracilis
Eur. J. Biochem.
184
353-359
1989
Escherichia coli, Euglena gracilis, Homo sapiens, Rattus norvegicus
Haedener, A.; Alefounder, P.; Hart, G.J.; Abell, C.; Battersby, A.R.
Investigation of putative active-site lysine residues in C
Biochem. J.
271
487-491
1990
Escherichia coli
Jordan, P.M; Warren, M.J.; Mgbeje, B.I.A.; Wood, S.P.; Cooper, J.B.; Louie, G.; Brownlie, P.; Lambert, R.; Blundell, T.L.
Crystallization and preliminary X-ray investigation of Escherichia coli porphobilinogen deaminase.
J. Mol. Biol.
224
269-271
1992
Escherichia coli
Haedener, A.; Matzinger, P.K.; Malashkevich, V.N.; Louie, G.V.; Wood, S.P.; Oliver, P.; Alefounder, P.R.; Pitt, A.R.; Abell, C.; Battersby, A.R.
Purification, characterization, crystallisation and X-ray analysis of selenomethionine-labelled hydroxymethylbilane synthase from Escherichia coli
Eur. J. Biochem.
211
615-624
1993
Escherichia coli
Juknat, A.A.; Doernemann, D.; Senger, H.
Purification and kinetic studies on a porphobilinogen deaminase from the unicellular green alga Scenedesmus obliquus
Planta
193
123-130
1994
Saccharomyces cerevisiae, Chlorella regularis, Escherichia coli, Euglena gracilis, Homo sapiens, Pisum sativum, Rattus norvegicus, Cereibacter sphaeroides, Tetradesmus obliquus, Spinacia oleracea
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