engleski

The Elusive 5'-Deoxyadenosyl Radical in Coenzyme-B12-Mediated Reactions

Vitamin B12 and its biologically active counterparts possess the only examples of carbon-cobalt bonds in living systems. The role of such motifs as radical reservoirs has potential application in future catalytic and electronic nano-devices. To fully understand radical generation in coenzyme B12 (dAdoCbl)-dependent enzymes, however, major obstacles still need to be overcome. In this work, we have used Car-Parrinello molecular dynamics (CPMD) simulations, in a mixed quantum mechanics/molecular mechanics (QM/MM) framework, to investigate the initial stages of the methylmalonyl-CoA-mutase-catalyzed reaction. We demonstrate that dAdoCbl and substrate activation occur in a stepwise manner, supporting the idea that the 5'-deoxyadenosyl radical (dAdo•) exists as a distinct entity in this reaction. We report free energy calculations and first-principles trajectories that help understand how B12 enzymes control highly reactive radical intermediates.

adenosylcobalamin; B12; CPMD; enzyme catalysis

nije evidentirano