spacer

Overview for MACiE Entry M0135

Version history

General Information

EC Number: 1.14.17.3 (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).

Catalytic CATH Codes:

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of oxygen

Image of ascorbate

Image of peptidylglycine

right arrow

Image of dehydroascorbate

Image of water

Image of peptidyl(2-hydroxyglycine)

oxygen
C00007
CHEBI:15379
ascorbate
C00072
CHEBI:38290
peptidylglycine
C02303
dehydroascorbate
C05422
CHEBI:17242
water
C00001
CHEBI:15377
peptidyl(2-hydroxyglycine)
C03718

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. [1].


View similar reactions


Stepwise Description of the Reaction

Step 1Ascorbate donates a single electron to one of the Cu(II) centres, which causes the hydroxide ligand to dissociate from the Cu(II) centre.
Step 2A 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 3One 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 4The 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 5In a homolytic substitution, the O-O bond is broken resulting in the hydroxylation of the peptide intermediate and the Cu(II) bound peroxo.
Step 6Water 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 7The two semidehydroascorbates disproportionate to yield ascorbate and dehydroascorbate [3].

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
His 108 A Side Chain
Gln 170 A Side Chain

Organic Cofactors for M0135

Type Identity Chain
Ascorbate ASC 0 Overview

Metal Cofactors for M0135

Type Het group Number Chain
copper CU 357 x Overview
copper CU 358 x Overview

References

  1. 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.
    Medline: 15080705
  2. S. T. Prigge et al. (1999), Nat. Struct. Biol., 6, 976-983. Substrate-mediated electron transfer in peptidylglycine alpha-hydroxylating monooxygenase.
    Medline: 10504734
  3. 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.
    Medline: 11028916
  4. S. T. Prigge et al. (2004), Science, 304, 864-867. Dioxygen binds end-on to mononuclear copper in a precatalytic enzyme complex.
    Medline: 15131304

Homologue information for M0135 (1sdw)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
catalytic activity (molecular function)
monooxygenase activity (molecular function)
peptidylglycine monooxygenase activity (molecular function)
copper ion binding (molecular function)
peptide metabolic process (biological process)
cellular process (biological process)
membrane (cellular component)
oxidation-reduction process (biological process)
spacer
spacer