The elusive 5'-deoxyadenosyl radical in coenzyme-B12-mediated reactions
2012 (English)In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 3, 1591-1599 p.Article in journal (Refereed) Published
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 nanodevices. 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 the 5'-deoxyadenosyl radical (dAdo(center dot)) 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 enzymes catalyze coenzyme activation and control highly reactive radical intermediates. that help understand how B12 enzymes catalyze coenzyme activation and control highly reactive radical intermediates.
Place, publisher, year, edition, pages
American Chemical Society , 2012. Vol. 134, no 3, 1591-1599 p.
IdentifiersURN: urn:nbn:se:liu:diva-76198DOI: 10.1021/ja207809bISI: 000301084400043OAI: oai:DiVA.org:liu-76198DiVA: diva2:513200
Funding Agencies|Australian Research Council||NZZ|02.03/63|Swiss Science Foundation||MSES|098-0982933-2937|EAM-FAU (Excellence Cluster)||NCI National Facility and Intersect Australia Ltd.||2012-03-312012-03-302012-07-31