Co²⁺/Co⁺Redox Tuning in Methyltransferases Induced by a Conformational Change at the Axial Ligand

Abstract

Density functional theory and quantum mechanics/molecular mechanics computations predict cob(I)alamin (Co(+)Cbx), a universal B(12) intermediate state, to be a pentacoordinated square pyramidal complex, which is different from the most widely accepted viewpoint of its tetracoordinated square planar geometry. The square pyramidality of Co(+)Cbx is inspired by the fact that a Co(+) ion, which has a dominant d(8) electronic configuration, forms a distinctive Co(+)--H interaction because of the availability of appropriately oriented filled d orbitals. This uniquely H-bonded Co(+)Cbx may have catalytic relevance in the context of thermodynamically uphill Co(2+)/Co(+) reduction that constitutes an essential component in a large variety of methyltransferases.

Reactions of Cobinamide with Glucose and Fructose

“…[12] Recent dispersion corrected DFT calculations showed the ability of Cbl(I) to form a weak bond with hydrogen atom of different molecules. [13] S. V. Makarov et al…”

Theoretical investigations of photophysics and spectroscopic properties in B12 cofactors.

“…Co(I)-H, thus adopting a square-pyramidal structure. 197,256,257 At present, the main sources of knowledge about cob(I)alamin are spectro- …”

Computational modeling of electronically excited states in cobalamin-dependent reactions.

“…This complexity is mainly due to the presence of a partially conjugated corrin macrocycle, which produces require the use of truncated models with respect to side chains and the nucleotide loop. [30][31][32][33] Structural models are typically derived directly from X-ray crystallographic data, [34][35][36][37][38] where the ligands are modified accordingly. Side chains of the corrin ring are replaced by hydrogen atoms, and the nucleotide loop containing the negatively charged PO4ion is omitted to afford a corrin model denoted B-[Co III (corrin)]-R + with a total charge of +1.…”

“…The full cofactor-based cob(II)alamin model is shown in Figure 1.4. 30,32,40 The enzyme-bound cob(I)alamin or "super-reduced" form is a d 8 high-spin complex that also produces the cob(II)alamin d 7 low-spin radical upon loss of an electron and attachment of the axial base. 40 Cob(I)alamin in its enzymebound conformation is a base-off cofactor, where oxidation of the cobalt ion leads to re-attachment of the axial base.…”

“…30,[104][105] Upon reduction, the Co(II)-based species forms a stable five-coordinate low-spin radical complex, where the unpaired electron resides entirely on the Co dz 2 orbital. 32 Cob(II)alamin has been characterized by x-ray, 89,106 and the structural features of the Co(II)-corrin moiety are similar to the biologically active forms of vitamin B12 (i.e., the Co(III)-corrins), with the exception of axial Co(II)-NDBI distances are generally shorter.…”