The nature and function of the catalytic centres of the DMSO reductases.
Density functional theory calculations have been performed to probe aspects of the function of the reaction centres of the DMSO reductase enzymes, in respect of catalysis of oxygen atom transfer (OAT). The first comparison between Mo and W at the active site of these enzymes has been accomplished by a consideration of the reaction profile for OAT from DMSO to [MoIV(OMe)(S2C2H2)2]1- versus that for the corresponding reaction with [WIV(OMe)(S2C2H2)2]1-. Both reaction profiles involve two transition states separated by a well-defined intermediate; however, whilst the second transition state (TS2) is clearly rate-limiting for the Mo system, the two transition states have a similar energy for the W system. The activation energy for OAT from DMSO to [WIV(OMe)(S2C2H2)2]1- is ca. 23 kJ mol-1 lower for the corresponding reaction with Mo, consistent with the significantly faster rate of reduction of DMSO by Rhodobacter capsulatus W-DMSO reductase than by its Mo counterpart. Consistent with the principle of the entatic state, the geometrical constraints imposed by the protein on the metal centre of the Mo- and W-DMSO reductases facilitate OAT by favouring a trigonal prismatic geometry for the transition state TS2 that is close to that observed for the metal in the oxidised form of each of these enzymes. The effects of different tautomers of a simplified form of the pyran ring-opened, dihydropterin state of the molybdopterin cofactor on the reaction profile for OAT have been considered. The major effect, a significant lowering of the activation barrier associated with TS2, is observed for a protonated form of a tautomer that involves conjugation between the pyrazine and metallodithiolene rings.
McNamara
Jonathan P
JP
School of Chemistry, University of Manchester, Manchester, UK M13 9PL.
Hillier
Ian H
IH
Bhachu
Tarnjeet S
TS
Garner
C David
CD
D001665:Binding Sites; D002384:Catalysis; D020134:Catalytic Domain; D003067:Coenzymes / Q000737:chemistry; D007506:Iron-Sulfur Proteins / Q000737:chemistry* / Q000378:metabolism*; D008667:Metalloproteins / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D000090006:Molybdenum Cofactors; D010088:Oxidoreductases / Q000737:chemistry* / Q000378:metabolism*; D011621:Pteridines / Q000737:chemistry; D013455:Sulfur / Q000737:chemistry
D003067:Coenzymes; D007506:Iron-Sulfur Proteins; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D010088:Oxidoreductases; D011621:Pteridines; D013455:Sulfur; C022261:molybdopterin; C045664:dimethyl sulfoxide reductase