Literature summary for 2.5.1.61 extracted from

Shoolingin-Jordan, P.M.; Al-Dbass, A.; McNeill, L.A.; Sarwar, M.; Butler, D.
Human porphobilinogen deaminase mutations in the investigation of the mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation (2003), Biochem. Soc. Trans., 31, 731-735.

Search for more literature for 2.5.1.61

Cloned(Commentary)

Cloned (Comment)	Organism
expression of wild-type and mutants in Escherichia coli strain BL21	Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
D99G	site-directed mutagenesis, inactive holo-enzyme mutant existing as a complex with 2 substrate molecules covalently bound to the dipyrromethane cofactor	Homo sapiens
additional information	the mutations of the enzyme cause acute intermittent porphyria	Homo sapiens
R149Q	site-directed mutagenesis, inactive apo-enzyme which is unable to assemble with the dipyrromethane cofactor, the mutant enzyme is unstable and heat-labile	Homo sapiens
R167Q	site-directed mutagenesis, mutation of active site residue, highly reduced activity compared to the wild-type enzyme, formation of stable enzyme-intermediate complexes	Homo sapiens
R173Q	site-directed mutagenesis, highly reduced activity compared to the wild-type enzyme, the major part of the enzyme exists as apo-enzyme without assembled dipyrromethane cofactor	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
4 porphobilinogen + H2O	Homo sapiens	third reaction step in heme biosynthesis pathway	1-hydroxymethylbilane + 4 NH3	-	?
additional information	Homo sapiens	mutations of the residues R167, R173, R149, and D99 of the enzyme cause acute intermittent porphyria, overview	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
4 porphobilinogen + H2O = hydroxymethylbilane + 4 NH3	catalytic cycle, cofactor assembly and tetrapyrrole chain polymerization mechanism, C261 is involved, residues D99 and R167 are essential for activity, overview	Homo sapiens	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
4 porphobilinogen + H2O	third reaction step in heme biosynthesis pathway	Homo sapiens	1-hydroxymethylbilane + 4 NH3	-	?
4 porphobilinogen + H2O	polymerization of 4 pyrrole molecules to a linear tetrapyrrole	Homo sapiens	hydroxymethylbilane + 4 NH3	i.e. pre-uroporphyrinogen, highly unstable compound	?
additional information	mutations of the residues R167, R173, R149, and D99 of the enzyme cause acute intermittent porphyria, overview	Homo sapiens	?	-	?

Synonyms

Synonyms	Comment	Organism
More	formerly EC 4.3.1.8	Homo sapiens
porphobilinogen deaminase	-	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
dipyrromethane	cofactor assembly mechanism, R149 and R173 are important, cofactor is produced from the apo-enzyme with pre-uroporphyrinogen	Homo sapiens

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Release 2023.1 (January 2023)