Naslov
The Activation of Coenzyme B12

Autori
Smith, David M. ; Bucher, Denis ; Sandala, Gregory M. ; Durbeej, Bo ; Radom, Leo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Invited Lectures of the Ninth Triennial Congress of the World Association of Theoretical and Computational Chemists / - , 2011, 220-220

Skup
The Ninth Triennial Congress of the World Association of Theoretical and Computational Chemists

Mjesto i datum
Santiago de Compostela, Španjolska, 16.07.2011. - 22.07.2011

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Adenosylcobalamin; B12; CPMD; Enzyme Catalysis

Sažetak
Enzymes that rely on coenzyme B12 (5’-deoxyadenosylcobalamin) have generated a great deal of interest in the scientific community. One particular focus has been the activation of the Co–C bond of the coenzyme and its connection to the subsequent hydrogen-atom abstraction from the substrate. In this contribution, we address these issues with a state-of-the-art QM/MM first principles molecular dynamics study of the methylmalonyl-CoA mutase catalysed reaction. Using techniques such as constrained- and meta-dynamics, we evaluate the free energy profiles associated with the initial steps of this reaction. By analysing the dynamics of the natural cofactor and two dideoxy analogues, we shed new light on the important catalytic effects as well as the way in which the enzyme controls the highly reactive 5’-deoxyadenosyl radical intermediate.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija, Biologija

POVEZANOST RADA