Co ~+-H interaction inspired alternate coordination geometries of biologically important cob(I)alamin: Possible structural and mechanistic consequences for methyltransferases (Conference Paper)

摘要

A detailed computational analysis employing density functional theory (DFT), atoms in molecules, and quantum mechanics/molecular mechanics (QM/MM) tools has been performed to investigate the primary coordination environment of cob(I)alamin (Co ~+Cbx), which is a ubiquitous B _(12) intermediate in methyltransferases and ATP: corrinoid adenosyltransferases. The DFT calculations suggest that the simplified (Co ~+Cbl) as well as the complete (Co ~+Cbi) complexes can adapt to the square pyramidal or octahedral coordination geometry owing to the unconventional H-bonding between the Co? ion and its axial ligands. These Co ~+-H bonds contain appreciable amounts of electrostatic, charge transfer, long-range correlation, and dispersion components. The computed reduction potentials of the Co ~(2+)/Co ~+ couple imply that the Co ~+-H(H _2O) interaction causes a greater anodic shift [5-98 mV vs. the normal hydrogen electrode (NHE) in chloroform solvent] than the analogous Co ~+-H(imidazole) interaction (1 mV vs. NHE) in the reduction potential of the Co ~(2+)/Co _+ couple. This may explain why a β-axial H _2O ligand has specifically been found in the active sites of certain methyltransferases. The QM/MM analysis of methionine synthase bound Co ~+Cbx (Protein Data Bank ID 1BMT, resolution 3.0 ?) indicates that the enzyme-bound Co ~+Cbx can also form a Co ~+-H bond, but can only exist in square pyramidal form because of the steric constraints imposed by the cellular environment. The present calculations thus support a recently proposed alternate mechanism for the enzyme-bound Co ~(2+)/Co ~+ reduction that involves the conversion of square pyramidal Co ~(2+)Cbx into square pyramidal Co ~+Cbx.