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

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

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

Izvornik
BIT's 3rd Annual World DNA and Genome Day / Mei, Xiaodan - Dalian, 2012, 50-50

Skup
BIT's 3rd Symposium on Enzymes and Biocatalysis

Mjesto i datum
Xi’an, Kina, 25.04.2012. - 28.04.2012

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
Coenzyme B12; QM/MM

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 steps with a state-of-the-art QM/MM first principles molecular dynamics study of the methylmalonyl-CoA mutase catalyzed reaction. Using techniques such as constrained- and meta-dynamics, we evaluate the free energy profiles and surfaces associated with the coenzyme cleavage and the substrate activation. By further analyzing the dynamics of the natural cofactor and two synthetic 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
Kemija

POVEZANOST RADA