The elusive 5'-deoxyadenosyl radical in coenzyme-B12-mediated reactions.
J Am Chem Soc
; 134(3): 1591-9, 2012 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-22229941
ABSTRACT
Vitamin B(12) 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 nanodevices. To fully understand radical generation in coenzyme B(12) (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 the 5'-deoxyadenosyl radical (dAdo(â¢)) exists as a distinct entity in this reaction, consistent with the results of extensive experimental and some previous theoretical studies. We report free energy calculations and first-principles trajectories that help understand how B(12) enzymes catalyze coenzyme activation and control highly reactive radical intermediates.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Propionibacterium
/
Vitamina B 12
/
Metilmalonil-CoA Mutase
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2012
Tipo de documento:
Article