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Overview for MACiE Entry M0122

Version history

General Information

EC Number: 1.8.4.11 (A member of the Oxidoreductases, Acting on a sulfur group of donors, With a disulfide as acceptor)

Enzyme Name: protein-methionine-S-oxide reductase

Biological Species: Bos taurus (Bovine)

Catalytic Chain UniprotKB Accession Codes:

  • P54149 - Mitochondrial peptide methionine sulfoxide reductase

Representative PDB Code: 1fva - CRYSTAL STRUCTURE OF BOVINE METHIONINE SULFOXIDE REDUCTASE (Resolution = 1.70 Å).

Catalytic CATH Codes:

  • 3.30.1060.10 - Peptide Methionine Sulfoxide Reductase; Chain A

Display structure information

Overall Reaction:

Image of thioredoxin

Image of protein L-methionine S-oxide

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Image of oxidised thioredoxin

Image of protein L-methionine

Image of water

thioredoxin
C00342
CHEBI:15967
protein L-methionine S-oxide
C03895
CHEBI:44120
oxidised thioredoxin
C00343
CHEBI:18191
protein L-methionine
C03023
CHEBI:16044
water
C00001
CHEBI:15377

Overall Comment: There are two alternative proposed mechanisms for the collapse of the covalently attached intermediate. One assumes that the collapse is facilitated by proton transfer from solvent or a residue to the oxygen atom of the intermediate and the attack of Cys218 on Cys72 [2 3]. The proposal shown in this entry corresponds to that in references 1 and 4 where reduction of methionine sulfoxide is shown to proceed through the formation of a sulfenic acid intermediate which has been characterised by chemical probes and mass spectrometry analyses.


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Stepwise Description of the Reaction

Step 1Cys72 initiates a nucleophilic attack on the sulfoxide in an addition reaction with concomitant deprotonation of Glu115.
Step 2Cys72 initiates a nucleophilic attack on the sulfenic acid in a substitution reaction, eliminating the protein L-methionine.
Step 3The hydroxyl group deprotonates Cys218, which initiates a nucleophilic attack on Cys72 in a substitution reaction, eliminating water.
Step 4Cys227 initiates a nucleophilic attack on Cys218 in a substitution reaction, eliminating Cys72.
Step 5Cys218 deprotonates one of the thiols of thioredoxin, which initiates a nucleophilic attack on Cys227 in a substitution reaction, eliminating Cys218.
Step 6Cys227 deprotonates the second thiol of thioredoxin, which initiates a nucleophilic attack on the sulfur of the thioredoxin that is covalently attached to Cys227 in a substitution reaction, eliminating Cys227.
Step 7Water deprotonates Cys227 in an inferred return step.

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Catalytic Residues Involved

Type Number Chain Location of Function
Cys 72 A Side Chain
Tyr 103 A Side Chain
Glu 115 A Side Chain
Tyr 155 A Side Chain
Cys 218 A Side Chain
Cys 227 A Side Chain

References

  1. F. Tete-Favier et al. (2000), Structure, 8, 1167-1178. Crystal structure of the Escherichia coli peptide methionine sulphoxide reductase at 1.9 A resolution.
    Medline: 11080639
  2. W. T. Lowther et al. (2000), Biochemistry, 39, 13307-13312. Structure and mechanism of peptide methionine sulfoxide reductase, an "anti-oxidation" enzyme.
    Medline: 11063566
  3. W. T. Lowther et al. (2000), Proc. Natl Acad. Sci. USA, 97, 6463-6468. Thiol-disulfide exchange is involved in the catalytic mechanism of peptide methionine sulfoxide reductase.
    Medline: 10841552
  4. S. Boschi-Muller et al. (2000), J. Biol. Chem., 275, 35908-35913. A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli.
    Medline: 10964927

Homologue information for M0122 (1fva)

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
mitochondrion (cellular component)
peptide-methionine (S)-S-oxide reductase activity (molecular function)
oxidoreductase activity (molecular function)
oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor (molecular function)
protein metabolic process (biological process)
oxidation-reduction process (biological process)
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