The Sulfur Shift: An Activation Mechanism for Periplasmic Nitrate Reductase and Formate Dehydrogenase

A structural rearrangement known
as sulfur shift occurs in some Mo-containing enzymes of the DMSO reductase
family. This mechanism is characterized by the displacement of a coordinating
cysteine thiol (or SeCys in Fdh) from the first to the second shell
of the Mo-coordination sphere metal. The hexa-coordinated Mo ion found
in the as-isolated state cannot bind directly any exogenous ligand
(substrate or inhibitors), while the penta-coordinated ion, attained
upon sulfur shift, has a free binding site for direct coordination
of the substrate. This rearrangement provides an efficient mechanism
to keep a constant coordination number throughout an entire catalytic
pathway. This mechanism is very similar to the carboxylate shift observed
in Zn-dependent enzymes, and it has been recently detected by experimental
means. In the present paper, we calculated the geometries and energies
involved in the sulfur-shift mechanism using QM-methods (M06/(6-311++G­(3df,2pd),SDD)//B3LYP/(6-31G­(d),SDD)).
The results indicated that the sulfur-shift mechanism provides an
efficient way to enable the metal ion for substrate coordination.