Literature summary for 1.14.17.3 extracted from

McIntyre, N.R.; Lowe, E.W.; Battistini, M.R.; Leahy, J.W.; Merkler, D.J.
Inactivation of peptidylglycine alpha-hydroxylating monooxygenase by cinnamic acid analogs (2016), J. Enzyme Inhib. Med. Chem., 31, 551-562 .

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Inhibitors

Inhibitors	Comment	Organism
(E)-(4-dimethylamino)cinnamic acid	-	Homo sapiens
(E)-3,4-methylenedioxycinnamic acid	-	Homo sapiens
(E)-4-aminocinnamic acid	-	Homo sapiens
2-trifluoromethylcinnamic acid	-	Homo sapiens
2-trifluoromethylcinnamic acid	-	Rattus norvegicus
3,4-methylenedioxycinnamic acid	-	Rattus norvegicus
3-(3-pyridyl)acrylic acid	-	Homo sapiens
3-(3-pyridyl)acrylic acid	-	Rattus norvegicus
4-aminocinnamic acid	-	Rattus norvegicus
4-nitrocinnamic acid	-	Rattus norvegicus
Cinnamic acid	extensive dialysis of bifunctional PAM incubated with cinnamate yielded inactive enzyme unable to catalyze the production of glyoxylate from hippuric acid	Homo sapiens
Cinnamic acid	-	Rattus norvegicus
additional information	cinnamic acid and cinnamic acid analogues are inhibitors or inactivators of PHM. The inactivation chemistry of the cinnamates exhibits all the attributes of a suicide-substrate. But no formation of an irreversible linkage between cinnamate and PHM in the inactivated enzyme is detected. Instead reversible formation of a Michael adduct between an active site nucleophile and cinnamate occurs that leads to inactive enzyme. Cinnamates are found in fruits, fruit juices, vegetables and flowers. Protection of PHM against the cinnamate-mediated inactivation by tiopronin. Molecular docking studies, overview	Homo sapiens
N,N-dimethyl-4-aminocinnamic acid	-	Rattus norvegicus
N-dansyl-4-aminocinnamate	a fluorescent molecule, an inactivator	Homo sapiens
N-dansyl-4-aminocinnamic acid	-	Rattus norvegicus
perdeuterated cinnamic acid	-	Homo sapiens
perdeuterated cinnamic acid	-	Rattus norvegicus
phenylpropionic acid	-	Rattus norvegicus
phenylpropynoic acid	i.e. phenylpropiolic acid	Homo sapiens
trans-cinnamic acid	-	Homo sapiens
Urocanic acid	-	Homo sapiens
Urocanic acid	-	Rattus norvegicus

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Cu2+	dependent on	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
peptidylglycine + ascorbate + O2	Homo sapiens	-	peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O	-	?
peptidylglycine + ascorbate + O2	Rattus norvegicus	the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones	peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P19021	-	-
Rattus norvegicus	P14925	-	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
acetyl-glycine + ascorbate + O2	-	Rattus norvegicus	?	-	?
hippuric acid + ascorbate + O2	-	Homo sapiens	benzamide + glyoxylate + dehydroascorbate + H2O	-	?
peptidylglycine + ascorbate + O2	-	Homo sapiens	peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O	-	?
peptidylglycine + ascorbate + O2	-	Rattus norvegicus	peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O	-	?
peptidylglycine + ascorbate + O2	the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones	Rattus norvegicus	peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O	-	?

Synonyms

Synonyms	Comment	Organism
PAM	-	Homo sapiens
PAM	-	Rattus norvegicus
peptidylglycine alpha-amidating monooxygenase	-	Rattus norvegicus
peptidylglycine alpha-hydroxylating monooxygenase	-	Homo sapiens
PHM	-	Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
6	-	assay at	Homo sapiens

Cofactor

Cofactor	Comment	Organism	Structure
ascorbate	-	Homo sapiens

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.01	-	N-dansyl-4-aminocinnamic acid	37°C, pH 6.0	Rattus norvegicus
0.2	-	2-trifluoromethylcinnamic acid	37°C, pH 6.0	Rattus norvegicus
0.3	-	3,4-methylenedioxycinnamic acid	37°C, pH 6.0	Rattus norvegicus
0.5	-	4-aminocinnamic acid	37°C, pH 6.0	Rattus norvegicus
0.6	-	4-nitrocinnamic acid	37°C, pH 6.0	Rattus norvegicus
2	-	phenylpropionic acid	37°C, pH 6.0	Rattus norvegicus
3	-	N,N-dimethyl-4-aminocinnamic acid	37°C, pH 6.0	Rattus norvegicus
4	-	Cinnamic acid	37°C, pH 6.0	Rattus norvegicus
4	-	perdeuterated cinnamic acid	37°C, pH 6.0	Rattus norvegicus
6	-	3-(3-pyridyl)acrylic acid	37°C, pH 6.0	Rattus norvegicus

General Information

General Information	Comment	Organism
metabolism	the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones	Rattus norvegicus
physiological function	peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme that catalyzes the final reaction in the maturation of alpha-amidated peptide hormones. Peptidylglycine alpha-hydroxylating monooxygenase (PHM) is the PAM domain responsible for the copper-, ascorbate- and O2-dependent hydroxylation of glycine-extended precursor peptides to the active alpha-amidated peptide and glyoxylate. Peptidylamidoglycolate lyase, EC 4.3.2.5, is the PAM domain responsible for the Zn(II)-dependent dealkylation of the alpha-hydroxyglycine-containing precursor to the final alpha-amidated peptide	Homo sapiens