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Literature summary for 1.14.17.3 extracted from

  • Abad, E.; Rommel, J.B.; Kaestner, J.
    Reaction mechanism of the bicopper enzyme peptidylglycine alpha-hydroxylating monooxygenase (2014), J. Biol. Chem., 289, 13726-13738 .
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.14.17.3

Metals/Ions

Metals/Ions Comment Organism Structure
Cu2+ a bicopper enzyme, two noninteracting copper atoms, involved in reaction mechanism, detailed overview Rattus norvegicus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
calcitonin + ascorbate + O2 Rattus norvegicus
-
 ? + dehydroascorbate + H2O
-
 ?
oxytoxin + ascorbate + O2 Rattus norvegicus
-
 ? + dehydroascorbate + H2O
-
 ?
peptidylglycine + ascorbate + O2 Rattus norvegicus
-
 peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
 ?
substance P + ascorbate + O2 Rattus norvegicus
-
 ? + dehydroascorbate + H2O
-
 ?
thyrotropin + ascorbate + O2 Rattus norvegicus
-
 ? + dehydroascorbate + H2O
-
 ?

Organism

Organism UniProt Comment Textmining
Rattus norvegicus P14925
-
-

Reaction

Reaction Comment Organism Reaction ID
[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) Rattus norvegicus
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
calcitonin + ascorbate + O2
-
 Rattus norvegicus ? + dehydroascorbate + H2O
-
 ?
oxytoxin + ascorbate + O2
-
 Rattus norvegicus ? + dehydroascorbate + H2O
-
 ?
peptidylglycine + ascorbate + O2
-
 Rattus norvegicus peptidyl(2-hydroxyglycine) + dehydroascorbate + H2O
-
 ?
substance P + ascorbate + O2
-
 Rattus norvegicus ? + dehydroascorbate + H2O
-
 ?
thyrotropin + ascorbate + O2
-
 Rattus norvegicus ? + dehydroascorbate + H2O
-
 ?

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
ascorbate
-
 Rattus norvegicus

General Information

General Information Comment Organism
additional information solvent-exposed active site of enzyme PHM Rattus norvegicus
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 Rattus norvegicus