Structure of the month - October 2014

Fig. 1. Dimer of the CoFeSP (enzyme) - RACo (activator) complex. The CoFeSP enzyme is shown as blue (large subunit) and yellow (small subunit) containing the (vitamin-)B12 cofactor. A dimer of RACo (pink) docks tightly with CoFeSP and clamps its B12 cofactor, shielding it from solvent (inset). Crucially, the β-ligand of B12 is replaced by the hydroxyl group of Ser-398 from RACo.

Figure 2. Proposed model for CoFeSP reactivation. Inactive CoFeSP-CO2+ is selectively bound by RACo (i), leading to the opening of its binding site for B12 (ii) and replacement of the β-ligand water with Ser-298 in RACo (iii). Ser-398 is then forced away from B12 through an ATP-driven movement in RACo (iv), transiently creating a tetra-coordinated Co2+ in B12, which is easily reduced to active Co1+ (v).

Table 1.