Overview for MACiE Entry M0135
EC Number: 220.127.116.11 (A member of the Oxidoreductases, Acting on paired donors, with O2 as oxidant and incorporation or reduction of oxygen. The oxygen incorporated need not be derived from O2, With reduced ascorbate as one donor, and incorporation of one atom of oxygen into the other donor)
Enzyme Name: peptidylglycine monooxygenase
Biological Species: Rattus norvegicus (Rat)
Catalytic Chain UniprotKB Accession Codes:
- P14925 - Peptidyl-alpha-hydroxyglycine alpha-amidating lyase
Representative PDB Code: 1sdw - REDUCED (CU+) PEPTIDYLGLYCINE ALPHA-HYDROXYLATING MONOOXYGENASE WITHBOUND PEPTIDE AND DIOXYGEN (Resolution = 1.85 Å).
Display structure information
It is unknown whether this reaction is reversible or not.
Overall Comment: There are several different alternative proposals for this mechanism. The two literature references cited propose very similar mechanisms. The mechanism depicted here corresponds to the one given by Chen et al. .
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Stepwise Description of the Reaction
|Step 1||Ascorbate donates a single electron to one of the Cu(II) centres, which causes the hydroxide ligand to dissociate from the Cu(II) centre.|
|Step 2||A second ascorbate donates a single electron to the other Cu(II) centre, which causes the water ligand to dissociate from the Cu(II) centre.|
|Step 3||One of the Cu(I) centres donates a single electron to a dioxygen molecule, which causes it to bind in a bidentate manner and displace the water ligand.|
|Step 4||The bound superoxide abstracts a hydrogen from the peptide substrate, and water displaces one of the bonds between the superoxide and the Cu(II) centre.|
|Step 5||In a homolytic substitution, the O-O bond is broken resulting in the hydroxylation of the peptide intermediate and the Cu(II) bound peroxo.|
|Step 6||Water coordinates to the Cu(I) centre, initiating a single electron relay through His108, Gln170, water and the peptide product to the Cu(II) centre, which then donates the electron to the bound oxo group, which deprotonates a water molecule to regenerate the active site.|
|Step 7||The two semidehydroascorbates disproportionate to yield ascorbate and dehydroascorbate .|
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Catalytic Residues Involved
||Location of Function
Organic Cofactors for M0135
Metal Cofactors for M0135
- P. Chen et al. (2004), J. Am. Chem. Soc., 126, 4991-5000. 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.
- S. T. Prigge et al. (1999), Nat. Struct. Biol., 6, 976-983. Substrate-mediated electron transfer in peptidylglycine alpha-hydroxylating monooxygenase.
- S. T. Prigge et al. (2000), Cell. Mol. Life Sci., 57, 1236-1259. New insights into copper monooxygenases and peptide amidation: structure, mechanism and function.
- S. T. Prigge et al. (2004), Science, 304, 864-867. Dioxygen binds end-on to mononuclear copper in a precatalytic enzyme complex.
Homologue information for M0135 (1sdw)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Links to this entry in other databases