Initial step of B12-dependent enzymatic catalysis: energetic implications regarding involvement of the one-electron-reduced form of adenosylcobalamin cofactor |
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Authors: | Pawel M Kozlowski Takashi Kamachi Manoj Kumar Kazunari Yoshizawa |
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Institution: | (1) Department of Chemistry, University of Louisville, Louisville, KY 40292, USA;(2) Institute for Materials Chemistry and Engineering, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan |
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Abstract: | Density functional theory analysis was performed to elucidate the impact of one-electron reduction upon the initial step of
adenosylcobalamin-dependent enzymatic catalysis. The transition state (TS) corresponding to the Co–C bond cleavage and subsequent
hydrogen abstraction from the substrate was located. The intrinsic reaction coordinate calculations predicted that the reaction
consisting of Co–C5′ bond cleavage in CoIII(corrin•)]–Rib (where Rib is ribosyl) and hydrogen-atom abstraction from the CH3–CH2–CHO substrate occurs in a concerted fashion. The computed activation energy barrier of the reaction (15.0 kcal/mol) was lowered
by approximately 54.5% in comparison with the reaction involving the positively charged cofactor model (Im–CoIII(corrin)]–Rib+, where Im is imidazole; energy barrier = 33.0 kcal/mol). The Im base was detached during the TS search in the reaction involving
the one-electron-reduced analogue. Thus, to compare the energetics of the two reactions, the axial Im ligand detachment energy
for the Im–CoIII(corrin•)]–Rib model was computed 7.6 kcal/mol (gas phase); 4.6 kcal/mol (water)]. Consequently, the effective activation energy
barrier for the reaction mediated by the Im-off CoIII(corrin•)]–Rib was estimated to be 22.6 kcal/mol, which implied an overall 31.5% reduction in the energetic demands of the reaction.
Considering that the lengthened Co–Naxial bond has been observed in X-ray crystal structure studies of B12-dependent mutases, the catalytic impact induced by one-electron reduction of the cofactor is expected to be higher in the
presence of the enzymatic environment. |
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