title: Co+-H interaction inspired alternate coordination geometries of biologically important cob(I)alamin: possible structural and mechanistic consequences for methyltransferases.
abstract: 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(2)O) 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(2)O 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 Å) 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 (Kumar and Kozlowski in Angew. Chem. Int. Ed. 50:8702-8705, 2011).
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, KY 40292, USA.
authors.forename: Manoj
authors.initials: M
authors.lastname: Kumar
authors.forename: Hajime
authors.initials: H
authors.lastname: Hirao
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kozlowski
mesh_terms: D020134:Catalytic Domain; D003035:Cobalt / Q000737:chemistry*; D018360:Crystallography, X-Ray; D008780:Methyltransferases / Q000737:chemistry*; D008958:Models, Molecular; D009247:NADH, NADPH Oxidoreductases / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D003035:Cobalt; C068157:aquacobalamin reductase; D009247:NADH, NADPH Oxidoreductases; D008780:Methyltransferases