Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Inorg Chem. 2012 Apr;17(4):611-9. doi: 10.1007/s00775-012-0881-4. Epub 2012 Feb 23.

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

Author information

1
Department of Chemistry, University of Louisville, Louisville, KY 40292, USA. pawel@louisville.edu

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.

PMID:
22358333
DOI:
10.1007/s00775-012-0881-4
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Support Center