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Information on EC 1.14.17.3 - peptidylglycine monooxygenase and Organism(s) Rattus norvegicus and UniProt Accession P14925
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1.14.17.3 peptidylglycine monooxygenaseIUBMB Comments
A copper protein. The enzyme binds two copper ions with distinct roles during catalysis. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalysed by EC 4.3.2.5 peptidylamidoglycolate lyase. In mammals, the two activities are part of a bifunctional protein. Involved in the final step of biosynthesis of alpha-melanotropin and related biologically active peptides.
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Word Map
- 1.14.17.3
-
glycine-extended
- neuropeptides
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beta-monooxygenase
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peptidyl-alpha-hydroxyglycine
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prohormone
- alpha-hydroxyglycine
- peptidylamidoglycolate
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endoproteolytic
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neurointermediate
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corticotrope
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ascorbate-dependent
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exafs
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4.3.2.5
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4-phenyl-3-butenoic
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noncoupled
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side-on
- dbetam
- medicine
- analysis
- synthesis
- pharmacology
The taxonomic range for the selected organisms is: Rattus norvegicus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
peptidylglycine alpha-hydroxylating monooxygenase, bifunctional pam, peptidyl-glycine alpha-amidating monooxygenase, peptidylglycine monooxygenase, alpha-ae, peptidylglycine alpha-amidating mono-oxygenase, phmcc, pam-b, peptidylglycine alpha-monooxygenase, peptidylglycine-alpha-amidating monooxygenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
peptidylglycine alpha-hydroxylating monooxygenase
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PAM
PAM-A
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PAM-B
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peptide alpha-amidating enzyme
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peptide alpha-amide synthase
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peptide-alpha-amide synthetase
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peptidyl alpha-amidating enzyme
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peptidylglycine 2-hydroxylase
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peptidylglycine alpha-amidating monooxygenase
peptidylglycine alpha-hydroxylase
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peptidylglycine alpha-hydroxylating monooxygenase
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synthase, peptide alpha-amide
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additional information
PAM
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PAM
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PAM consists of O2-sensitive PHM and peptidyl-alpha-hydroxyglycine alpha-amidating lyase, PAL, activities
peptidylglycine alpha-amidating monooxygenase
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peptidylglycine alpha-amidating monooxygenase
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bifunctional enzyme: peptidylglycine alpha-hydroxylating monooxygenase and peptigylamidoglycolate lyase
additional information
the 2-step process is catalyzed by only 1 enzyme called type A peptidylglycine alpha-amidating enzyme
additional information
-
EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PHM), 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PHL)
additional information
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EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PHM), 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PHL)
additional information
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EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PHM), 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase (PHL)
additional information
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the 2-step process is catalyzed by only 1 enzyme called type A peptidylglycine alpha-amidating enzyme
additional information
-
the 2-step process is catalyzed by only 1 enzyme called type A peptidylglycine alpha-amidating enzyme
additional information
-
the 2-step process is catalyzed by only 1 enzyme called type A peptidylglycine alpha-amidating enzyme
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
equilibrium ordered mechanism in which substrate binds prior to oxygen
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
reaction mechanism simulation using quantum mechanics/molecular mechanics calculations, molecular dynamics simulations, and the enzyme crystal structure, PDB 1SDW, detailed overview. The overall reaction of PHM consists of a stereospecific hydroxylation of the pro-S hydrogen using molecular O2 as oxygen source. Two electrons and two protons are consumed during the reaction. Ascorbate is the best (but not the only possible) reductant. In the protein resting state, both copper atoms are in the +2 oxidation state and are reduced by ascorbate to +1. Molecular oxygen then binds to CuM as the substrate binds to the protein. first and rate-limiting step is hydrogen abstraction, second step is OH rebinding via double protonated intermediate and transition state (TS2)
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
stopped-flow studies of the reduction of the copper centers suggest a bifurcated electron transfer pathway in peptidylglycine monooxygenase
[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
sequential activity of 2 enzymes contained within a bifunctional protein
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
equilibrium ordered mechanism
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
kinetic model for slow-binding inhibition
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
structural analysis of mutant H172A, binding of ligands CO, Cu2+
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
structural analysis
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
kinetic analysis
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
bifunctional enzyme showing peptidylglycine alpha-hydroxylating monooxygenase, EC 1.14.17.3, and peptidylamidoglycolate lyase, PAL, EC 4.3.2.5, activities, the enzyme possesses 2 catalytic domains
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
bifunctional enzyme showing peptidylglycine alpha-hydroxylating monooxygenase, PHM, EC 1.14.17.3, and peptidylamidoglycolate lyase, PAL, EC 4.3.2.5, activities
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
cleavage of CN bond in N-acetylated glycines, R-CO-NH-CH2-COOH, e.g. found in neuropeptide prohormones
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
detailed analysis of the reaction mechanism, reaction scheme, strictly ordered ping-pong kinetic mechanism in which ascorbate first reduces Cu(II) to Cu(I), semidehydroascorbate being released, after which the peptide binds and finally oxygen, active site structure
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
detailed analysis of the reaction mechanism, role of noncoupled nature of the active site
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
equilibrium-ordered and steady-state-random or -ordered reaction mechanism for the wild-type and the mutant Y318F enzyme, respectively, active site Y318 is involved, C-H bond activation is dominated by quantum mechanical tunneling, peptide substrate binding structure at the active site
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
inter-copper electron transfer, interdomain structure
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[peptide]-glycine + 2 ascorbate + O2 = [peptide]-(2S)-2-hydroxyglycine + 2 monodehydroascorbate + H2O
mechanism, substrate binding structure
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
O-dealkylation
O-oxidative dealkylation of benzaldehyde imino-oxy acetic acid
redox reaction
oxidation
reduction
redox reaction
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oxidation
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reduction
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SYSTEMATIC NAME
IUBMB Comments
[peptide]-glycine,ascorbate:oxygen oxidoreductase (2-hydroxylating)
A copper protein. The enzyme binds two copper ions with distinct roles during catalysis. Peptidylglycines with a neutral amino acid residue in the penultimate position are the best substrates for the enzyme. The product is unstable and dismutates to glyoxylate and the corresponding desglycine peptide amide, a reaction catalysed by EC 4.3.2.5 peptidylamidoglycolate lyase. In mammals, the two activities are part of a bifunctional protein. Involved in the final step of biosynthesis of alpha-melanotropin and related biologically active peptides.
CAS REGISTRY NUMBER
COMMENTARY
90597-47-0
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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
(([(1E)-phenylmethylidene]amino)oxy)acetic acid + ascorbate + O2
(2R)-hydroxy(([(1E)-phenylmethylidene]amino)oxy)ethanoic acid + ?
non-enzymatic dealkylation yields benzaldoxime and glyoxylate
-
-
?
Ac-Tyr-Val-Gly + ascorbate + O2
Ac-Tyr-Val-(2-OH-Gly) + dehydroascorbate + H2O
-
-
-
?
benzaldehyde imino-oxy acetic acid + O2
benzaldoxime + glyoxylate
assay at 37°C, pH 6.0
-
-
?
dansyl-D-Tyr-Val-Gly + ascorbate + O2
dansyl-D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
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-
-
?
diiodotyrosylglycine + ascorbate + O2
diiodotyrosyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
N-dansyl-Tyr-Val-Gly + ascorbate + O2
(S)-N-dansyl-Tyr-Val-alpha-hydroxyglycine + dehydroascorbate + H2O
-
-
-
ir
N-[(2-phenylcyclopropyl)carbonyl]glycine + ascorbate + O2
N-[(2-phenylcyclopropyl)carbonyl]-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
r
proopiomelanocortin peptide + ascorbate + O2
proopiomelanocortin peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
adrenocorticotrophic hormone(9-14) + ascorbate + O2
adrenocorticotrophic hormone(9-13)-2-hydroxyglycine + dehydroascorbate + H2O
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-
-
?
alpha-N-acetyl-adrenocorticotrophic hormone(1-14) + ascorbate + O2
alpha-N-acetyl-adrenocorticotrophic hormone(1-13)-2-hydroxyglycine + dehydroascorbate + H2O
alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
D-Tyr-Val-Gly + ascorbate + O2
D-Tyr-Val-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
dansyl-D-Tyr-Val-Gly + ascorbate + O2
dansyl-D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
dansyl-D-Tyr-Val-Gly + H2O2
dansyl-D-Tyr-Val-2-hydroxyglycine + H2O
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peptidylglycine monooxygenase is able to catalyze the hydroxylation of peptidylglycine substrates starting from the oxidized enzyme and using hydrogen peroxide as the only source of oxygen
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?
dansyl-Gly-Gly-Ser-CO-NH-CH2-COOH + ascorbate + O2
?
-
substrate contains either protium or deuterium at the CH2-group
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-
?
gamma-Glu-Gly-Gly + ascorbate + O2
gamma-Glu-Gly-NH2 + glyoxylate + dehydroascorbate + H2O
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?
glutathione + ascorbate + O2
gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
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?
hippuric acid + ascorbate + O2
? + dehydroascorbate + H2O
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C-H bond cleavage is irreversible, protiated and dideuterated substrate
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-
ir
HOOC-NH-CH2-COOH + ascorbate + O2
?
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substrate contains either protium or deuterium at the CH2-group
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?
monoiodo-alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
monoiodo-alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
monoiodo-D-Tyr-Val-Gly + ascorbate + O2
monoiodo-D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
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synthetic peptid
-
?
N-(2,4,6-trinitrophenyl)-D-Tyr-Val-Gly + ascorbate + O2
N-(2,4,6-trinitrophenyl)-D-Tyr-Val-(2-hydroxyglycine) + dehydroascorbate + H2O
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-
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?
N-acetyl-Tyr-Val-Gly + ascorbate + O2
N-acetyl-Tyr-Val-(2-hydroxyglycine) + dehydroascorbate + H2O
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-
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?
N-acetylglycine + 2 ascorbate + O2
N-acetyl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
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?
N-acetylglycine + ascorbate + O2
acetylamine + glyoxylate + dehydroascorbate + H2O
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?
N-acetylglycine + ascorbate + O2
N-acetyl(2-hydroxyglycine) + dehydroascorbate + H2O
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?
N-benzoylglycine + ascorbate + O2
N-benzoyl(2-hydroxyglycine) + dehydroascorbate + H2O
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?
N-butyrylglycine + 2 ascorbate + O2
N-butyryl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
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?
N-Dan-Tyr-Val-Gly + ascorbate + O2
N-Dan-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
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PAM activity assay, the product is unstable and dismutates to N-Dan-Tyr-Val-NH2 and glyoxylate (EC4.3.2.5)
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?
N-dansyl-L-Tyr-L-Val-Gly + ascorbate + O2
N-dansyl-L-Tyr-L-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
-
?
N-decanoylglycine + 2 ascorbate + O2
N-decanoyl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
-
-
-
-
?
N-decanoylglycine + ascorbate + O2
decanoylamine + glyoxylate + dehydroascorbate + H2O
-
-
-
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?
N-hexanoylglycine + 2 ascorbate + O2
N-hexanoyl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
-
-
-
-
?
N-hexanoylglycine + ascorbate + O2
hexanoylamine + glyoxylate + dehydroascorbate + H2O
-
-
-
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?
N-octanoylglycine + 2 ascorbate + O2
N-octanoyl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
-
-
-
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?
N-propionylglycine + 2 ascorbate + O2
N-propionyl-2-hydroxyglycine + 2 semidehydroascorbate + H2O
-
-
-
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?
N-trifluoroacetylglycine + ascorbate + O2
N-trifluoroacetyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
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?
peptidylglycine + 2 ascorbate + O2
peptidyl(2-hydroxyglycine) + 2 semidehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxylglycine) + dehydroascorbate + H2O
-
peptidylglycine alpha-hydroxylating monooxygenase reaction
the carbinol is the substrate for the peptidylamidoglycolate lyase reaction, EC 4.3.2.5, forming glyoxylate and amidated peptide
-
?
Phe-Gly-Phe-Gly + ascorbate + O2
Phe-Gly-Phe-(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
-
?
S-(1,2-dicarboxyethyl)-glutathione + ascorbate + O2
S-(1,2-dicarboxyethyl)-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-(4-nitrobenzyl)-glutathione + ascorbate + O2
S-(4-nitrobenzyl)-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-butyl-glutathione + ascorbate + O2
S-butyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-decyl-glutathione + ascorbate + O2
S-decyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-ethyl-glutathione + ascorbate + O2
S-ethyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-hexyl-glutathione + ascorbate + O2
S-hexyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-methyl-glutathione + ascorbate + O2
S-methyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-octyl-glutathione + ascorbate + O2
S-octyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
S-propyl-glutathione + ascorbate + O2
S-propyl-gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones
-
-
?
proopiomelanocortin peptide + ascorbate + O2
proopiomelanocortin peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
a POMC 18-kDa fragment
-
-
?
proopiomelanocortin peptide + ascorbate + O2
proopiomelanocortin peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
a POMC 18-kDa fragment, establishment of an assay method
-
-
?
alpha-N-acetyl-adrenocorticotrophic hormone(1-14) + ascorbate + O2
alpha-N-acetyl-adrenocorticotrophic hormone(1-13)-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
alpha-N-acetyl-adrenocorticotrophic hormone(1-14) + ascorbate + O2
alpha-N-acetyl-adrenocorticotrophic hormone(1-13)-2-hydroxyglycine + dehydroascorbate + H2O
-
inhibitory substrate
-
r
alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
D-Tyr-Val-Gly + ascorbate + O2
D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
D-Tyr-Val-Gly + ascorbate + O2
D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
D-Tyr-Val-Gly + ascorbate + O2
D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
-
?
D-Tyr-Val-Gly + ascorbate + O2
D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
synthetic peptid
-
?
dansyl-D-Tyr-Val-Gly + ascorbate + O2
dansyl-D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
-
?
dansyl-D-Tyr-Val-Gly + ascorbate + O2
dansyl-D-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
stereospecific
-
-
?
hippuric acid + ascorbate + O2
alpha-hydroxyhippuric acid + dehydroascorbate + H2O
-
i.e. N-benzoylglycine
-
?
hippuric acid + ascorbate + O2
alpha-hydroxyhippuric acid + dehydroascorbate + H2O
-
i.e. N-benzoylglycine
-
?
monoiodo-alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
monoiodo-alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
monoiodo-alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
monoiodo-alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
monoiodo-alpha-N-acetyl-Tyr-Val-Gly + ascorbate + O2
monoiodo-alpha-N-acetyl-Tyr-Val-2-hydroxyglycine + dehydroascorbate + H2O
-
-
-
?
peptidyl-glycine + ascorbate + O2
peptidyl-(2-hydroxylglycine) + dehydroascorbate + H2O
-
-
-
-
?
peptidyl-glycine + ascorbate + O2
peptidyl-(2-hydroxylglycine) + dehydroascorbate + H2O
-
PHM catalyzes the stereospecific hydroxylation of the glycine alpha-carbon of all peptidylglycine substrates
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
requirement for O2
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
requirement for O2
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
requirement for O2
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
requirement for O2
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
COOH-terminal glycine
semidehydroascorbate
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
peptidylglycine alpha-hydroxylating monooxygenase reaction
the carbinol is the substrate for the peptidylamidoglycolate lyase reaction, EC 4.3.2.5, forming glyoxylate and amidated peptide
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
2 Cu2+, A and B, are involved in the catalytic reaction
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
C-H bond cleavage is irreversible, activation of molecular O2 and of the C-H bond of the substrate, mechanism, reductive activation of Cu(II)-OOH to generate a reactive copper-oxo species
-
-
ir
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
formation of a CuIIM-OOH intermediate, intramolecular electron transfer
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
peptidylglycine alpha-hydroxylating monooxygenase reaction, diverse glycine derivatives or substitutes
the carbinol is the substrate for the peptidylamidoglycolate lyase reaction, EC 4.3.2.5, forming glyoxylate and amidated peptide
-
?
R-CO-NH-CH2-COOH + ascorbate + O2
R-CO-NH2 + CHO-COOH + dehydroascorbate + H2O
-
-
-
-
?
R-CO-NH-CH2-COOH + ascorbate + O2
R-CO-NH2 + CHO-COOH + dehydroascorbate + H2O
-
via hydroxylated reaction intermediates
-
-
?
additional information
?
-
constitutive-like secretion of POMC products in recombinant enzyme-expressing cells
-
-
?
additional information
?
-
peptidylglycine alpha-hydroxylating monooxygenase (PHM) catalyzes stereospecific alpha-C hydroxylation of C-terminal glycines, the first step in the alpha-amidation of hormones, growth factors and neurotransmitters. The molecular oxygen-dependent reaction requires two equivalents of ascorbate as exogenous reductant, releasing water and semidehydroascorbate as byproducts
-
-
?
additional information
?
-
-
cleavage of C-H bond in the second reaction step is irreversible
-
-
?
additional information
?
-
-
EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PMH) and 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase
-
-
?
additional information
?
-
-
EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PMH) and 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase
-
-
?
additional information
?
-
-
EC 1.14.17.3 is often called peptidylglycine alpha-amidating monooxygenase (PAM) and the alpha-amidated product is mentioned as the product of the reaction, but the alpha-amidation of glycine-extended peptides is a two-step process catalyzed by 2 enzymes: 1. EC 1.14.17.3: production of peptidyl(2-hydroxyglycine) by a copper, molecular oxygen and ascorbate-dependent peptidyl-glycine alpha-hydroxylating monooxygenase (PMH) and 2. conversion of the peptidyl-alpha-hydroxyglycine derivative into an alpha-amidated product at physiological pH by peptidyl-alpha-hydroxyglycine alpha-amidating lyase
-
-
?
additional information
?
-
-
substrates are also physiologically relevant peptides related to alpha-melanotropine
-
-
?
additional information
?
-
-
tunneling of hydrogen ion, relatively flexible
-
-
?
additional information
?
-
-
cleavage of CN bond in N-acetylated glycines, R-CO-NH-CH2-COOH, e.g. found in neuropeptide prohormones, inhibition of the enzyme leads to a decrease in alpha-aminated peptide production and accumulation of glycine-extended precursors
-
-
?
additional information
?
-
-
enzyme catalyzes the biosynthesis of peptide hormones through radical cleavage of the C-terminal glycine residues of the corresponding prohormones
-
-
?
additional information
?
-
-
enzyme catalyzes the production of neurohormones and neurotransmitters
-
-
?
additional information
?
-
-
enzyme is involved in peptide posttranslational activation
-
-
?
additional information
?
-
-
enzyme is required for amidation of autocrine growth factors causing proliferation in tumor cells
-
-
?
additional information
?
-
-
enzyme might be involved in secretory vesicle budding and fusion in the cardiac ANP-secretory pathway
-
-
?
additional information
?
-
-
substrate specificity, cleavage of CN bond in N-acetylated glycines, R-CO-NH-CH2-COOH, e.g. found in neuropeptide prohormones
-
-
?
additional information
?
-
-
substrate specificity, effects of substitutions on the glycine substrate, overview
-
-
?
additional information
?
-
-
long distance electron-transfer mechanism between the two distant copper cations, a perfect fitting for a water bridge, molecular dynamics simulations using wild-type and mutant enzymes, overview
-
-
?
additional information
?
-
-
PAM is the rate-limiting enzyme for the generation of carboxy-terminal alpha-amidated neuropeptides
-
-
?
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
proopiomelanocortin peptide + ascorbate + O2
proopiomelanocortin peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
a POMC 18-kDa fragment
-
-
?
glutathione + ascorbate + O2
gamma-Glu-Cys-NH2 + glyoxylate + dehydroascorbate + H2O
-
-
-
-
?
peptidyl-glycine + ascorbate + O2
peptidyl-(2-hydroxylglycine) + dehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxylglycine) + dehydroascorbate + H2O
-
peptidylglycine alpha-hydroxylating monooxygenase reaction
the carbinol is the substrate for the peptidylamidoglycolate lyase reaction, EC 4.3.2.5, forming glyoxylate and amidated peptide
-
?
R-CO-NH-CH2-COOH + ascorbate + O2
R-CO-NH2 + CHO-COOH + dehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
-
-
-
?
peptidylglycine + ascorbate + O2
peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
peptidylglycine alpha-hydroxylating monooxygenase reaction
the carbinol is the substrate for the peptidylamidoglycolate lyase reaction, EC 4.3.2.5, forming glyoxylate and amidated peptide
-
?
additional information
?
-
constitutive-like secretion of POMC products in recombinant enzyme-expressing cells
-
-
?
additional information
?
-
-
cleavage of CN bond in N-acetylated glycines, R-CO-NH-CH2-COOH, e.g. found in neuropeptide prohormones, inhibition of the enzyme leads to a decrease in alpha-aminated peptide production and accumulation of glycine-extended precursors
-
-
?
additional information
?
-
-
enzyme catalyzes the biosynthesis of peptide hormones through radical cleavage of the C-terminal glycine residues of the corresponding prohormones
-
-
?
additional information
?
-
-
enzyme catalyzes the production of neurohormones and neurotransmitters
-
-
?
additional information
?
-
-
enzyme is involved in peptide posttranslational activation
-
-
?
additional information
?
-
-
enzyme is required for amidation of autocrine growth factors causing proliferation in tumor cells
-
-
?
additional information
?
-
-
enzyme might be involved in secretory vesicle budding and fusion in the cardiac ANP-secretory pathway
-
-
?
additional information
?
-
-
PAM is the rate-limiting enzyme for the generation of carboxy-terminal alpha-amidated neuropeptides
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ascorbate
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
copper
Cu2+
copper
Cu2+
Zn2+
additional information
Ag(I) is iso-electronic with Cu(I) and has been shown to be handled by similar cellular transport processes. Although complexes of Ag in the Ag(III) state exists, the instability of the Ag(II) state renders the metal unsuitable for a functional substitute for copper in enzymes such as PHM. When enzyme mutants H107A/H108A and M109I (a wild-type analogue with both copper sites intact) are incubated with excess AgNO3, each variant binds a single Ag(I) ion, from which it is inferred that Ag(I) binds selectively at the M-center with little or no affinity for the H-center
copper
two distinct Cu centers are located in the protein active site. Of the two distinct Cu centers in the protein active site (separated by 11 A), the CuH site, believed to serve primarily as an electron transfer site, is coordinated by three histidines, H107, H108, H172, in a roughly T-shaped geometry. The CuM site, where oxygen binding and hydroxylation occur, has a mixed coordination sphere consisting of two histidines, H242, and H244, and a methionine, M314. Reaction mechanism, overview. Reaction of wild-type enzyme PHM with CO (an oxygen analogue) produces the M-site CO complex, which shows a unique XES spectrum that can be computationally reproduced by including interactions between Cu(I) and the CO ligand. The valence-to-core (VtC) region can serve as a probe of not only ligand speciation, but also offer insight into the coordination geometry, in a fashion similar to XAS pre-edges, and may be sufficiently sensitive to the coordination of exogenous ligands to be useful in the study of reaction mechanisms. Application of X-ray emission spectroscopy to copper proteins via a study of a series of mixed His-Met copper sites where the ligand set varies in a systematic way between the His3 and Met3 limits. The sites are derived from the wild-type peptidylglycine monooxygenase (PHM), two single-site variants which replicate each of its two copper sites (CuM-site and CuH-site), and the transporters CusF and CusB. Structure analysis of copper centers of wild-type and mutant enzymes
Cu2+
a bicopper enzyme, two noninteracting copper atoms, involved in reaction mechanism, detailed overview
Cu2+
a dicopper enzyme, copper reconstitution of recombinant purified wild-type and mutant enzymes, modeling of the active site structure of PHM showing the M-center and H-center with substrate, overview
Cu2+
a pair of uncoupled copper centers separated by 11 A termed CuH and CuM, an unusual Cu(I)S-Met interaction at the oxygen binding M-site, and the postulated Cu(II)-superoxo intermediate, structure and chemistry of the individual metal centers. The copper centers are involved in the catalytic mechanism, the M-center binds two histidines and a methionine at all pHs, while the H-center is two-coordinate at neutral pH but coordinated another methionine S ligand at low pH. Analysis of CO complex formations of wild-type and mutant enzymes at pH 3.5-7.5, detailed overview
Cu2+
dependent on, two coopper ions, CuM is coordinated by His242, His244 and Met314, while CuH is bound to His107, His108, and His172. The catalytic reaction requires both copper ions to cycle between Cu(II) and Cu(I) oxidation states. Two conformations at CuM in which the second CO band depends on the mode of substrate binding and may thus report on a substrate-induced catalytically active configuration. Upon substrate addition, the lower (nyCO) band is amplified while the other decreases, but not at a 1:1 ratio, indicating an equilibrium which is shifted in the presence of substrate. Crystal structure of CuM and CuH sites, overview
Cu2+
the cuproenzyme PAM requires copper to catalyze peptide amidation
copper
-
dependent on, copper-deficiency decreases the enzyme activity, tissue copper status, overview
copper
-
inter-copper electron transfer, mechanism, structure, 2 copper atoms per enzyme
Cu2+
-
mutant H172A has reduced copper content: below 0.3 Cu2+ per protein molecule
Cu2+
-
oxygen activation by the noncoupled binuclear copper site, analysis of structure and electron transfer mechanism, formation of a CuIIM-OOH reaction intermediate, thermodynamics
Cu2+
-
required, reductive activation of Cu(II)-OOH to generate a reactive copper-oxo species
Cu2+
-
a copper enzyme, copper binding ratios of recombinant catalytic core, overview
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
EDTA
recombinant enzyme, alpha-hydroxylation activity can be restored by Mn2+, Zn2+, Cd2+, and Co2+, but not by Ca2+, Cu2+, Mg2+, and Fe3+
ascorbate
-
above 0.4 mM for the purified enzyme, above 1.5 mM for the enzyme in crude extract
4-Phenyl-3-butenoic acid
-
binds to the lumenal side of the enzyme where the peptidylglycine alpha-hydroxylating PHM activity is localized
additional information
-
inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals, diverse glycine derivatives or substitutes, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
O2
substrate binding triggers oxygen activation in peptidylglycine monooygenase
additional information
-
enzyme expression is induced by androgen-deprivation therapy
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.78
H2O2
-
100 mM MES, pH 5.5, 0.2 mM dansyl-D-Tyr-Val-Gly, 5 microM CuSO4, H2O2
0.0025
N-Dan-Tyr-Val-Gly
-
PHM activity in the soluble fraction of control and intermittent hypoxia brain stem ectracts
0.0051
dansyl-D-Tyr-Val-Gly
-
100 mM MES, pH 5.5, 0.2 mM dansyl-D-Tyr-Val-Gly, 5 microM CuSO4, ascorbate
0.8
dansyl-D-Tyr-Val-Gly
-
100 mM MES, pH 5.5, 0.2 mM dansyl-D-Tyr-Val-Gly, 5 microM CuSO4, 1 mM H2O2
0.0012
N-acetyl-Tyr-Val-Gly
-
purified recombinant wild-type enzyme, pH 7.0
0.0063
N-acetyl-Tyr-Val-Gly
-
purified recombinant wild-type enzyme, pH 5.5
0.009
peptidylglycine
-
transiently expressed mutants Q170N and Q170L, pH 5.5
0.018
peptidylglycine
-
transiently expressed mutants Q170A and Y79W, pH 5.5
additional information
additional information
stopped-flow reduction kinetics of wild-type and mutant enzymes using the chromophoric agent N,N-dimethyl-4-phenylenediamine (DMPD) as the reductant, overview
-
additional information
additional information
-
Km for D-Tyr-Val-Gly depends on concentration of ascorbate, Km for ascorbate is constant over a wide range of D-Tyr-Val-Gly concentration
-
additional information
additional information
-
competitive and noncompetitive kinetic isotope effects in wild-type enzyme and mutant Y318F, kinetic mechanism
-
additional information
additional information
-
fluorescence spectroscopic analysis of intrinsic tryptophan
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5
(25R)-3beta-hydroxycholest-5-en-27-oate
-
100 mM MES, pH 5.5, 0.2 mM dansyl-D-Tyr-Val-Gly, 5 microM CuSO4, H2O2
9.2
N-dansyl-L-Tyr-L-Val-Gly
-
100 mM MES, pH 5.5, 0.2 mM dansyl-D-Tyr-Val-Gly, 5 microM CuSO4, ascorbate
-
additional information
additional information
-
intrinsic rate constants for wild-type and mutant Y318F enzyme
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
very low activity in H9c2 cells, no ascorbate in assay mixture
additional information
-
very low activity in crude subcellular preparations
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.5 - 5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4 - 9
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
peptidylglycine alpha-amidating monooxygenase activity in copper-deficient lactating dams is reduced to 15% compared to controls. Pups fed by copper-deficient dams showed an earlier decrease of peptidylglycine alpha-amidating monooxygenase activity throughout lactation
additional information
-
-
additional information
Atp7a, AP-1, and PAM co-localize in the Golgi region of primary pituitary cells
additional information
-
enzyme expression level in different tissues in copper adequate and deficient status, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
quantification of PAM endocytic trafficking to the trans-Golgi network
additional information
-
distribution of membrane-bound and soluble peptidylglycine alpha-hydroxylating activity
-
-
transmembrane protein with lumenal and cytoplasmic parts, overview, abundant in atrial secretory vesicles
-
from atrial myocytes, enzyme is recruited by aggregates of pro-atrial natriuretic peptide proANP, N-terminally deleted proANP is inhibited in recruiting the enzyme
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
disruption of AP-1-dependent late endosomal trafficking diminishes the ability of PAM to retain copper and produce amidated peptides. Impaired AP-1 function alters luminal copper delivery to PAM. Altered luminal cuproenzyme function may contribute to diseases associated with diminished AP-1 function. Reduced AP-1 function makes 18-kDa fragment amidation more sensitive to inhibition by bathocuproine disulfonate, a cell-impermeant Cu(I) chelator. The endocytic trafficking of PAM is altered, and PAM-1 accumulates on the cell surface when AP-1 levels are reduced
metabolism
the enzyme catalyzes the final reaction in the maturation of alpha-amidated peptide hormones
physiological function
additional information
physiological function
in neuroendocrine cells, ATP7A provides copper to peptidylglycine alpha-amidating monooxygenase (PAM), an essential enzyme that requires copper to catalyze peptide amidation, one of the final steps in the production of bioactive peptides. Trafficking of Atp7a, a copper pump, and the cuproenzyme PAM-1 depend on adaptor protein-1 complex (AP-1). The enzyme is involved in the prohormone POMC processing pathway and constitutive-like secretion, overview. Production of the amidated products of POMC (18-kDa fragment-NH2, JP-NH2, and ACTH(1-13)NH2) requires both PAM and Atp7a, Atp7a concentrates in the Golgi region in pituitary cells
physiological function
peptidylglycine alpha-hydroxylating monooxygenase catalyzes the generation of C-terminal carboxamides of peptide hormones, neurotransmitters, and growth factors for biological activation. The enzyme is a noninteracting bicopper enzyme that stereospecifically hydroxylates the terminal glycine of small peptides for its later amidation. Neuroendocrine messengers, such as oxytocin, rely on the biological activity of this enzyme. Each catalytic turnover requires one oxygen molecule, two protons from the solvent, and two electrons
additional information
structure of the PHM enzyme active site taken from PDB ID 1OPM structure with bound substrate diiodotyrosylglycine: the H-site coordinates to the Ndelta atom of H107, H108, and Nepsilon of H172, and the oxygen binding (catalytic) M-site coordinates to Nepsilon of H242 and H244 and the thiother S of M314. The side chain of the conserved E313 forms an H-bond to the main chain amide nitrogen of H244
additional information
substrate binding triggers oxygen activation in peptidylglycine monooygenase
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). AMD_RAT
976
2
108675
Swiss-Prot
Secretory Pathway (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
110000
-
x * 125000, PAM-1, SDS-PAGE, x * 110000, PAM-2, SDS-PAGE, x * 90000, PAM-3, SDS-PAGE
125000
-
x * 125000, PAM-1, SDS-PAGE, x * 110000, PAM-2, SDS-PAGE, x * 90000, PAM-3, SDS-PAGE
35000
-
PHM, proteolytic processed, determined by SDS-PAGE and Western blot analysis
75000
90000
-
x * 125000, PAM-1, SDS-PAGE, x * 110000, PAM-2, SDS-PAGE, x * 90000, PAM-3, SDS-PAGE
additional information
additional information
-
PAM in particulate fraction of H9c2 cells contains 86, 76, and 46 kDa proteins, soluble PAM fraction contains 110, 86, and 46 kDa proteins
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
additional information
-
enzyme PAM-1, the longest transcript, is composed of, at the lumenal side, the peptidylglycine alpha-hydroxylating monooxygenase PHM catalytic domain, a noncatalytic domain from exon A, the peptidyl-alpha-hydroxyglacine alpha-amidating lyase PAL catalytic domain, a transmembrane domain, and a C-terminal cytoplasmic domain, deletion of exon A yields PAM-2, further deletion of the transmembrane domain yields soluble PAM-3 within the vesicle lumen
?
-
x * 125000, PAM-1, SDS-PAGE, x * 110000, PAM-2, SDS-PAGE, x * 90000, PAM-3, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
partially glycosylated, at Asn 660, recombinant enzyme from mouse cells
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations based onthe crystal structure 1SDW, overview
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
H107A
H107A/H108A
H108A
H172A
site-directed mutagenesis, comparison of stopped-flow reduction kinetics of wild-type and mutant enzymes
H242A
M109I
site-directed mutagenesis, altered reaction with CO compared to wild-type
M314H
site-directed mutagenesis, altered reaction with CO compared to wild-type
M314I
site-directed mutagenesis, the CuM site mutant which has an empty M site in the reduced state, does not react with CO in the presence or absence of peptide substrate
H172A
H242A
-
mutation in the copper center of domain two, no activity in presence of H2O2
Q170A
Q170E
Q170L
Q170N
Y318F
-
site-directed mutagenesis, active site residue mutant, slightly reduced rate constant for C-H bond cleavage compared to the wild-type enzyme
Y79W
additional information
H107A
site-directed mutagenesis, altered reaction with CO compared to wild-type
H107A
site-directed mutagenesis, comparison of stopped-flow reduction kinetics of wild-type and mutant enzymes
H107A/H108A
site-directed mutagenesis, comparison of stopped-flow reduction kinetics of wild-type and mutant enzymes
H107A/H108A
site-directed mutagenesis, removal of two of three histidines prevents metal binding at the H-center, the double His mutant H107H108A binds copper only in the M-site and therefore contains about 1 equivalent copper per protein. The PHM variant, when metalated, binds copper and silver at only a single center
H107A/H108A
site-directed mutagenesis, structure analysis of copper centers compared to wild-type
H107A/H108A
site-directed mutagenesis, the double His mutant H107H108A binds copper only in the M-site and therefore contains about 1 equivalent copper per protein
H108A
site-directed mutagenesis, altered reaction with CO compared to wild-type
H108A
site-directed mutagenesis, comparison of stopped-flow reduction kinetics of wild-type and mutant enzymes
H242A
site-directed mutagenesis, comparison of stopped-flow reduction kinetics of wild-type and mutant enzymes
H242A
site-directed mutagenesis, structure analysis of copper centers compared to wild-type
H242A
site-directed mutagenesis, the CuM site mutant which has an empty M site in the reduced state, does not react with CO in the presence or absence of peptide substrate
H242A
site-directed mutagenesis, the CuM site mutant which has an empty M site in the reduced state, does not react with CO in the presence or absence of peptide substrate. The PHM variant, when metalated, binds copper and silver at only a single center. The H242A variant is an M-site deletion mutant that removes one of the two histidines necessary for tight binding of copper to the M-site
H172A
-
mutant of copper ligand of peptidylglycine alpha-hydroxylating enzyme, reduced copper content below 0.3 Cu2+ per protein molecule
H172A
-
mutation in the copper center of domain one, no activity in presence of H2O2
Q170A
-
site-directed, PCR-based mutagenesis, altered Km compared to the wild-type enyme
Q170A
-
site-directed mutagenesis, mutant enzyme activity as a function of the number of hydrogen bonds established in the bridge between the two copper ions compared to the wild-type enzyme
Q170E
-
site-directed, PCR-based mutagenesis, kinetics similar to the wild-type enyme
Q170E
-
site-directed mutagenesis, mutant enzyme activity as a function of the number of hydrogen bonds established in the bridge between the two copper ions compared to the wild-type enzyme
Q170L
-
site-directed, PCR-based mutagenesis, kinetics similar to the wild-type enyme
Q170L
-
site-directed mutagenesis, mutant enzyme activity as a function of the number of hydrogen bonds established in the bridge between the two copper ions compared to the wild-type enzyme
Q170N
-
site-directed, PCR-based mutagenesis, kinetics similar to the wild-type enyme
Q170N
-
site-directed mutagenesis, mutant enzyme activity as a function of the number of hydrogen bonds established in the bridge between the two copper ions compared to the wild-type enzyme
Y79W
-
site-directed, PCR-based mutagenesis, altered kinetics compared to the wild-type enzyme, highly reduced activity
Y79W
-
site-directed mutagenesis, mutant enzyme activity as a function of the number of hydrogen bonds established in the bridge between the two copper ions compared to the wild-type enzyme
additional information
comparison of the first electron transfer step (reductive phase) in the wild-type enzyme PHM as well as its mutant variants. Stopped-flow is used to record the reduction kinetic traces using the chromophoric agent N,N-dimethyl-4-phenylenediamine (DMPD) as the reductant
additional information
-
only the residues 42-356 carrying the monoogenase domain was expressed
additional information
-
only the residues 42-356 carrying the monoogenase domain was expressed
additional information
-
large scale production of the enzyme using an automated bioreactor, method optimization and evaluation, overview
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
rapid inactivation of recombinant enzyme at acidic pH in vitro
438566
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
substance-P, i.e. RPKPQQFFGLM-NH2, protects against inactivation by sulfite
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant wild-type and mutant enzymes from CHO DG44 cells. Copper reconstitution of recombinant purified wild-type and mutant enzymes
large scale purification of the recombinant truncated enzyme, comprising the catalytic core residues 42-356, from CHO DG44 cells, reconstitution of copper bound to the enzyme
-
mutant H172A of type A alpha-AE, recombinant from chinese hamster ovary cells
-
recombinant wild-type and mutant enzymes from CHO cells by a 3-step chromatographic method
-
type A alpha-AE, recombinant from chinese hamster ovary cells
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene PAM-1, recombinant stable expression in murine AtT-20 cells. Atp7a, AP-1, and PAM co-localize in the Golgi region of recombinant AtT-20 cells
medullary thyroid alpha-AE, type A, expression in chinese hamster ovary cells
recombinant expression of wild-type and mutant enzymes in CHO DG44 cells
expression of the truncated enzyme, comprising the catalytic core residues 42-356, in CHO DG44 cells
-
medullary thyroid alpha-AE, type A, expression in chinese hamster ovary cells
-
medullary thyroid carcinoma enzyme, expression in mouse C 127 cells via bovine papilloma virus vector, amino acid and DNA sequence analysis
-
single copy gene, alternative splicing generates several forms of enzyme mRNA, overview
-
transient expression of wild-type and mutant enzymes in HEK293 cells, stable expression of wild-type and mutant enzymes in CHO cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase via reactive oxygen species-mediated proteolytic processing
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
PHM is a potential target for the development of inhibitors as drugs for the treatment of human disease
pharmacology
-
enzyme is an attractive target for development of anti-tumor compounds
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Glembotski, C.C.
Further characterization of the peptidyl alpha-amidating enzyme in rat anterior pituitary secretory granules
Arch. Biochem. Biophys.
241
673-683
1985
Rattus norvegicus
Beaudry, G.A.; Mehta, N.M.; Ray, M.I.; Bertelsen, A.H.
Purification and characterization of functional recombinant alpha-amidating enzyme secreted from mammalian cells
J. Biol. Chem.
265
17694-17699
1990
Rattus norvegicus
Merkler, D.J.; Young, S.D.
Recombinant type A rat 75-kDa alpha-amidating enzyme catalyzes the conversion of glycine-extended peptides to peptide amides via an alpha-hydroxyglycine intermediate
Arch. Biochem. Biophys.
289
192-196
1991
Rattus norvegicus
Glembotski, C.C.; Eipper, B.A.; Mains, R.E.
Characterization of a peptide alpha-amidation activity from rat anterior pituitary
J. Biol. Chem.
259
6385-6392
1984
Rattus norvegicus
Mehta, N.M.; Gilligan, J.P.; Jones, B.N.; Bertelsen, A.H.; Roos, B.A.; Birnbaum, R.S.
Purification of a peptidylglycine alpha-amidating enzyme from transplantable rat medullary thyroid carcinomas
Arch. Biochem. Biophys.
261
44-54
1988
Rattus norvegicus
Oyarce, A.M.; Eipper, B.A.
Neurosecretory vesicles contain soluble and membrane-associated monofunctional and bifunctional peptidylglycine alpha-amidating monoxygenase proteins
J. Neurochem.
60
1105-1114
1993
Rattus norvegicus
Girard, B.; Ouafik, L.; Boudouresque, F.
Characterization and regulation of peptidylglycine alpha-amidating monooxygenase (PAM) expression in H9c2 cardiac myoblasts
Cell Tissue Res.
298
489-497
1999
Rattus norvegicus
Merkler, D.J.; Kulathila, R.; Francisco, W.A.; Ash, D.E.; Bell, J.
The irreversible inactivation of two copper-dependent monooxygenases by sulfite: peptidylglycine alpha-amidating enzyme and dopamine beta-monooxygenase
FEBS Lett.
366
165-169
1995
Rattus norvegicus
Bell, J.; Ash, D.E.; Snyder, L.M.; Kulathila, R.; Blackburn, N.J.; Merkler, D.J.
Structural and functional investigations on the role of zinc in bifunctional rat peptidylglycine alpha-amidating enzyme
Biochemistry
36
16239-16246
1997
Rattus norvegicus (P14925)
Jaron, S.; Blackburn, N.J.
Characterization of a half-apo derivative of peptidylglycine monooxygenase. Insight into the reactivity of each active site copper
Biochemistry
40
6867-6875
2001
Rattus norvegicus
Francisco, W.A.; Merkler, D.J.; Blackburn, N.J.; Klinman, J.P.
Kinetic mechanism and intrinsic isotope effects for the peptidylglycine alpha-amidating enzyme reaction
Biochemistry
37
8244-8252
1998
Rattus norvegicus
Jaron, S.; Mains, R.E.; Eipper, B.A.; Blackburn, N.J.
The catalytic role of the copper ligand H172 of peptidylglycine alpha-hydroxylating monooxygenase (PHM): a spectroscopic study of the H172A mutant
Biochemistry
41
13274-13282
2002
Rattus norvegicus
Francisco, W.A.; Knapp, M.J.; Blackburn, N.J.; Klinman, J.P.
Hydrogen tunneling in peptidylglycine alpha-hydroxylating monooxygenase
J. Am. Chem. Soc.
124
8194-8195
2002
Rattus norvegicus
Miller, L.A.; Baumgart, L.E.; Chew, G.H.; deLong, M.A.; Galloway, L.C.; Jung, K.W.; Merkler, K.A.; Nagle, A.S.; Poore, D.D.; Yoon, C.H.; Merkler, D.J.
Glutathione, S-substituted glutathiones, and leukotriene C4 as substrates for peptidylglycine alpha-amidating monooxygenase
Arch. Biochem. Biophys.
412
3-12
2003
Rattus norvegicus
Prohaska, J.R.; Gybina, A.A.; Broderius, M.; Brokate, B.
Peptidylglycine-alpha-amidating monooxygenase activity and protein are lower in copper-deficient rats and suckling copper-deficient mice
Arch. Biochem. Biophys.
434
212-220
2005
Mus musculus, Rattus norvegicus
Francisco, W.A.; Blackburn, N.J.; Klinman, J.P.
Oxygen and hydrogen isotope effects in an active site tyrosine to phenylalanine mutant of peptidylglycine alpha-hydroxylating monooxygenase: mechanistic implications
Biochemistry
42
1813-1819
2003
Rattus norvegicus
Bell, J.; El Meskini, R.; D'Amato, D.; Mains, R.E.; Eipper, B.A.
Mechanistic investigation of peptidylglycine alpha-hydroxylating monooxygenase via intrinsic tryptophan fluorescence and mutagenesis
Biochemistry
42
7133-7142
2003
Rattus norvegicus
Labrador, V.; Brun, C.; Konig, S.; Roatti, A.; Baertschi, A.J.
Peptidyl-glycine alpha-amidating monooxygenase targeting and shaping of atrial secretory vesicles: inhibition by mutated N-terminal ProANP and PBA
Circ. Res.
95
98-109
2004
Rattus norvegicus
Francisco, W.A.; Wille, G.; Smith, A.J.; Merkler, D.J.; Klinman, J.P.
Investigation of the pathway for inter-copper electron transfer in peptidylglycine alpha-amidating monooxygenase
J. Am. Chem. Soc.
126
13168-13169
2004
Rattus norvegicus
Barratt, B.J.; Easton, C.J.; Henry, D.J.; Li, I.H.; Radom, L.; Simpson, J.S.
Inhibition of peptidylglycine alpha-amidating monooxygenase by exploitation of factors affecting the stability and ease of formation of glycyl radicals
J. Am. Chem. Soc.
126
13306-13311
2004
Rattus norvegicus
Chen, P.; Solomon, E.I.
Oxygen activation by the noncoupled binuclear copper site in peptidylglycine alpha-hydroxylating monooxygenase. Reaction mechanism and role of the noncoupled nature of the active site
J. Am. Chem. Soc.
126
4991-5000
2004
Rattus norvegicus
Owen, T.C.; Merkler, D.J.
A new proposal for the mechanism of glycine hydroxylation as catalyzed by peptidylglycine alpha-hydroxylating monooxygenase (PHM)
Med. Hypotheses
62
392-400
2004
Rattus norvegicus
Bauman, A.T.; Jaron, S.; Yukl, E.T.; Burchfiel, J.R.; Blackburn, N.J.
pH Dependence of peptidylglycine monooxygenase. Mechanistic implications of Cu-methionine binding dynamics
Biochemistry
45
11140-11150
2006
Rattus norvegicus
Prohaska, J.R.; Broderius, M.
Plasma peptidylglycine alpha-amidating monooxygenase (PAM) and ceruloplasmin are affected by age and copper status in rats and mice
Comp. Biochem. Physiol. B
143
360-366
2006
Mus musculus, Rattus norvegicus
Crespo, A.; Marti, M.A.; Roitberg, A.E.; Amzel, L.M.; Estrin, D.A.
The catalytic mechanism of peptidylglycine alpha-hydroxylating monooxygenase investigated by computer simulation
J. Am. Chem. Soc.
128
12817-12828
2006
Rattus norvegicus (P14925)
Bauman, A.T.; Yukl, E.T.; Alkevich, K.; McCormack, A.L.; Blackburn, N.J.
The hydrogen peroxide reactivity of peptidylglycine monooxygenase supports a Cu(II)-superoxo catalytic intermediate
J. Biol. Chem.
281
4190-4198
2006
Rattus norvegicus
Bauer, J.D.; Sunman, J.A.; Foster, M.S.; Thompson, J.R.; Ogonowski, A.A.; Cutler, S.J.; May, S.W.; Pollock, S.H.
Anti-inflammatory effects of 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester, potential inhibitors of neuropeptide bioactivation
J. Pharmacol. Exp. Ther.
320
1171-1177
2007
Rattus norvegicus
Bauman, A.T.; Ralle, M.; Blackburn, N.J.
Large scale production of the copper enzyme peptidylglycine monooxygenase using an automated bioreactor
Protein Expr. Purif.
51
34-38
2007
Rattus norvegicus
de la Lande, A.; Marti, S.; Parisel, O.; Moliner, V.
Long distance electron-transfer mechanism in peptidylglycine alpha-hydroxylating monooxygenase: a perfect fitting for a water bridge
J. Am. Chem. Soc.
129
11700-11707
2007
Rattus norvegicus
Merkler, D.J.; Asser, A.S.; Baumgart, L.E.; Carballo, N.; Carpenter, S.E.; Chew, G.H.; Cosner, C.C.; Dusi, J.; Galloway, L.C.; Lowe, A.B.; Lowe, E.W.; King, L.; Kendig, R.D.; Kline, P.C.; Malka, R.; Merkler, K.A.; McIntyre, N.R.; Romero, M.; Wilcox, B.J.; Owen, T.C.
Substituted hippurates and hippurate analogs as substrates and inhibitors of peptidylglycine alpha-hydroxylating monooxygenase (PHM)
Bioorg. Med. Chem.
16
10061-10074
2008
Blattella germanica, Homo sapiens, Rattus norvegicus (P14925)
McIntyre, N.R.; Lowe, E.W.; Merkler, D.J.
Imino-oxy acetic acid dealkylation as evidence for an inner-sphere alcohol intermediate in the reaction catalyzed by peptidylglycine alpha-hydroxylating monooxygenase
J. Am. Chem. Soc.
131
10308-10319
2009
Rattus norvegicus (P14925)
Sharma, S.D.; Raghuraman, G.; Lee, M.S.; Prabhakar, N.R.; Kumar, G.K.
Intermittent hypoxia activates peptidylglycine alpha-amidating monooxygenase in rat brain stem via reactive oxygen species-mediated proteolytic processing
J. Appl. Physiol.
106
12-19
2009
Rattus norvegicus
Chufan, E.E.; Prigge, S.T.; Siebert, X.; Eipper, B.A.; Mains, R.E.; Amzel, L.M.
Differential reactivity between two copper sites in peptidylglycine alpha-hydroxylating monooxygenase
J. Am. Chem. Soc.
132
15565-15572
2010
Rattus norvegicus
McIntyre, N.R.; Lowe, E.W.; Belof, J.L.; Ivkovic, M.; Shafer, J.; Space, B.; Merkler, D.J.
Evidence for substrate preorganization in the peptidylglycine alpha-amidating monooxygenase reaction describing the contribution of ground state structure to hydrogen tunneling
J. Am. Chem. Soc.
132
16393-16402
2010
Rattus norvegicus
Chauhan, S.; Kline, C.D.; Mayfield, M.; Blackburn, N.J.
Binding of copper and silver to single-site variants of peptidylglycine monooxygenase reveals the structure and chemistry of the individual metal centers
Biochemistry
53
1069-1080
2014
Rattus norvegicus (P14925)
Chauhan, S.; Hosseinzadeh, P.; Lu, Y.; Blackburn, N.J.
Stopped-flow studies of the reduction of the copper centers suggest a bifurcated electron transfer pathway in peptidylglycine monooxygenase
Biochemistry
55
2008-2021
2016
Rattus norvegicus (P14925)
Kline, C.D.; Blackburn, N.J.
Substrate-induced carbon monoxide reactivity suggests multiple enzyme conformations at the catalytic copper M-center of peptidylglycine monooxygenase
Biochemistry
55
6652-6661
2016
Rattus norvegicus (P14925)
Martin-Diaconescu, V.; Chacon, K.N.; Delgado-Jaime, M.U.; Sokaras, D.; Weng, T.C.; DeBeer, S.; Blackburn, N.J.
Kbeta valence to core X-ray emission studies of Cu(I) binding proteins with mixed methionine-histidine coordination. Relevance to the reactivity of the M- and H-sites of peptidylglycine monooxygenase
Inorg. Chem.
55
3431-3439
2016
Rattus norvegicus (P14925)
Abad, E.; Rommel, J.B.; Kaestner, J.
Reaction mechanism of the bicopper enzyme peptidylglycine alpha-hydroxylating monooxygenase
J. Biol. Chem.
289
13726-13738
2014
Rattus norvegicus (P14925)
Bonnemaison, M.L.; Baeck, N.; Duffy, M.E.; Ralle, M.; Mains, R.E.; Eipper, B.A.
Adaptor protein-1 complex affects the endocytic trafficking and function of peptidylglycine alpha-amidating monooxygenase, a luminal cuproenzyme
J. Biol. Chem.
290
21264-21279
2015
Rattus norvegicus (P14925), Homo sapiens (P19021)
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