Dimethylsulfoxide reductase

 

The molybdoenzyme dimethylsulfoxide (DMSO) reductase contributes to the release of dimethylsulfide, a compound that has been implicated in cloud nucleation and global climate regulation. Terminal reductase during anaerobic growth on various sulfoxide and N-oxide compounds. This enzyme contains a mononuclear Mo coordinated by two molybdopterin guanine dinucleotides as its single cofactor.

 

Reference Protein and Structure

Sequence
Q57366 UniProt (1.7.2.3, 1.8.5.3) IPR006658 (Sequence Homologues) (PDB Homologues)
Biological species
Rhodobacter sphaeroides (Bacteria) Uniprot
PDB
1eu1 - THE CRYSTAL STRUCTURE OF RHODOBACTER SPHAEROIDES DIMETHYLSULFOXIDE REDUCTASE REVEALS TWO DISTINCT MOLYBDENUM COORDINATION ENVIRONMENTS. (1.3 Å) PDBe PDBsum 1eu1
Catalytic CATH Domains
3.40.50.740 CATHdb (see all for 1eu1)
Cofactors
Molybdenum(6+) (1)
Click To Show Structure

Enzyme Reaction (EC:1.8.5.3)

menaquinone
CHEBI:16374ChEBI
+
dimethyl sulfide
CHEBI:17437ChEBI
+
water
CHEBI:15377ChEBI
→
menaquinol
CHEBI:18151ChEBI
+
dimethyl sulfoxide
CHEBI:28262ChEBI
Alternative enzyme names: DMSO reductase, Dimethylsulfoxide reductase,

Enzyme Mechanism

Introduction

The active site of DMSO reductase contains a mononuclear Mo coordinated by two molybdopterin guanine dinucleotides and the oxygen of Ser147as its single cofactor. The oxidative half cycle of the reaction is initiated by substrate binding to the reduced enzyme, forming the Ered.DMSO complex containing Mo(IV). This is stabilised by Y114. Binding of DMSO is via the oxygen and leads to some degree of lengthening of the S-O bond. In the catalytic step, the substrate oxygen is transferred as an oxo ligand to the Mo with a concomitant two-electron oxidation of the metal forming Mo(VI) and dimethyl sulfate which is then released from the active site. The reductive half cycle of the reaction consists of two one-electron reduction steps coupled to the transfer of two protons to generate H2O from the substrate derived oxo group. This reduces Mo(VI) to Mo(IV) . The water is lost to the solvent and the oxidised enzyme is therefore returned to its initial reduced state.

Catalytic Residues Roles

UniProt PDB* (1eu1)
Tyr156 Tyr114A Stabilises the intermediate Ered.DMSO complex by hydrogen bonding to the O atom. electrostatic stabiliser
Trp158 Trp116A Prevents water binding to Mo causing loss of the Q pterin group leading to inactivation of the enzyme steric role
*PDB label guide - RESx(y)B(C) - RES: Residue Name; x: Residue ID in PDB file; y: Residue ID in PDB sequence if different from PDB file; B: PDB Chain; C: Biological Assembly Chain if different from PDB. If label is "Not Found" it means this residue is not found in the reference PDB.

Chemical Components

References

  1. George GN et al. (2007), Inorg Chem, 46, 3097-3104. Interaction of Product Analogues with the Active Site ofRhodobacterSphaeroidesDimethyl Sulfoxide Reductase. DOI:10.1021/ic0619052. PMID:17361996.
  2. Cobb N et al. (2007), J Biol Chem, 282, 35519-35529. Spectroscopic and Kinetic Studies of Y114F and W116F Mutants of Me2SO Reductase from Rhodobacter capsulatus. DOI:10.1074/jbc.m704458200. PMID:17921142.
  3. Schindelin H et al. (1996), Science, 272, 1615-1621. Crystal Structure of DMSO Reductase: Redox-Linked Changes in Molybdopterin Coordination. DOI:10.1126/science.272.5268.1615. PMID:8658134.

Step 1.

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Catalytic Residues Roles

Residue Roles
Tyr114A electrostatic stabiliser
Trp116A steric role

Chemical Components

Step 1.

Contributors

Gemma L. Holliday