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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1ff3
Original Entry
Title:
Oxidoreductase
Compound:
Peptide methionine sulfoxide reductase
Mutant:
No
UniProt/Swiss-Prot:
P27110-MSRA_ECOLI
EC Class:
1.8.4.6
Other CSA Entries:
Overview of all sites for 1ff3
Homologues of 1ff3
Entries for UniProt/Swiss-Prot: P27110
Entries for EC: 1.8.4.6
Other Databases:
PDB entry: 1ff3
PDBsum entry: 1ff3
UniProt/Swiss-Prot: P27110
IntEnz entry: 1.8.4.6
Literature Report:
Introduction:
Peptide methionine sulphoxide reductase (PMSR) is from Escherichia coli. It catalyses the reduction of oxidised methionine residues in proteins. It is implicated in the defence of organisms against oxidative stress and in the regulation of processes involving peptide methionine oxidation/reduction.
Mechanism:
1. Nucleophilic attack of Cys 51 on the sulphur atom of the substrate sulphoxide leads to the formation of a tetrahedral intermediate.
2. Rearrangement of this intermediate results in the release of a Met molecule,
and the formation of a sulphenate ion.
3. The sulphenate ion oxygen atom is protonated presumably by a water molecule.
4. The sulphenate ion is protonated by protonated Glu 94 at the same time as being nucleophilically attacked by Cys 198. This leads to the release of a water molecule, and the formation of a transient disulphide bond between Cys 51
and Cys 198.
5. Cys 206 then nucleophilically attacks Cys 198, breaking the disulphide bond between Cys 198 and Cys 51, and forming a new one between Cys 198 and Cys 206.
6. Return of the active site to a fully reduced state requires either a DTT or thioredoxin regenerating system.
Sites:

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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CASA 51 52Sidechain
NucleophileSubstrate
Cys 51 acts as a nucleophile by attacking the sulphur atom of the sulphoxide substrate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11080639 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11080639 Current protein Mutagenesis of residue
PubMed ID 11080639 Current protein Conservation of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLUA 94 95Sidechain
Acid/baseResidue
Acts as a general acid to protonate the sulphenate ion at the same time as Cys 198 nucleophilically attacks.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11080639 Current protein Conservation of residue
PubMed ID 11080639 Current protein Residue is positioned appropriately (ligand position known)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CYSA 198 199Sidechain
NucleophileResidue
Cys 198 nucleophilically attacks the sulphur atom of Cys 51 to form a disulphide bridge.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10964927 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10964927 Current protein Mutagenesis of residue

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
CYSA 206 207Sidechain
NucleophileResidue
Cys 206 nucleophilically attacks Cys 198 to form a dulsphide bridge, releasing Cys 51.
Evidence from paper Evidence concerns Evidence type
PubMed ID 10964927 Current protein Structural similarity to homologue of known mechanism
PubMed ID 10964927 Current protein Mutagenesis of residue
Notes:
Cys 51 to Cas 51 isn't a proper mutation, it's the result of crystallisation.
Tyr 82 and Tyr 134 are possibly catalytic and probably stabilise the negative charge on the intermediate, however there is not enough evidence to favour this prediction.
References:
1
Crystal structure of the Escherichia coli peptide methionine sulphoxide reductase at 1.9 A resolution.
F. TĂȘte-Favier and D. Cobessi and S. Boschi-Muller and S. Azza and G. Branlant and A. Aubry
Structure 8, (11) 1167-78, (2000).
11080639
2
A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli.
S. Boschi-Muller and S. Azza and S. Sanglier-Cianferani and F. Talfournier and A. Van Dorsselear and G. Branlant
J Biol Chem 275, (46) 35908-13, (2000).
10964927
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