Reductive elimination pathway for homocysteine to methionine conversion in cobalamin-dependent methionine synthase.

Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry
Pawel M KozlowskiKazunari Yoshizawa

Abstract

Density functional theory has been applied to investigate the methyl transfer from methylcobalamin (MeCbl) cofactor to homocysteine (Hcy) as catalyzed by methionine synthase (MetH). Specifically, the S(N)2 and the reductive elimination pathways have been probed as the possible mechanistic pathways for the methyl transfer reaction. The calculations indicate that the activation barrier for the reductive elimination reaction (24.4 kcal mol(-1)) is almost four times higher than that for the S(N)2 reaction (7.3 kcal mol(-1)). This high energy demand of the reductive elimination pathway is rooted in the structural distortion of the corrin ring that is induced en route to the formation of the triangular transition state. Furthermore, the reductive elimination reaction demands the syn accommodation of the methyl group and the substrate over the upper face of the corrin ring, which also accounts for the high energy demand of the reaction. Consequently, the reductive elimination pathway for MetH-catalyzed methyl transfer from MeCbl to Hcy cannot be considered as one of the possible mechanistic routes.

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Oct 29, 2011·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Pawel M KozlowskiKazunari Yoshizawa

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Citations

Dec 10, 2015·Dalton Transactions : an International Journal of Inorganic Chemistry·Yoshitsugu MoritaTakashi Hayashi
Feb 3, 2021·Journal of Molecular Graphics & Modelling·Szymon MalinowskiPawel M Kozlowski
Jan 15, 2014·Chemical Reviews·Margareta R A BlombergPer E M Siegbahn

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