Download MendeleyA Thiamine-Dependent Enzyme Utilizes an Active Tetrahedral Intermediate in Vitamin K Biosynthesis
Song, H.G., Dong, C., Qin, M.M., Chen, Y.Z., Sun, Y.R., Liu, J.J., Chan, W., Guo, Z.H.(2016) J Am Chem Soc 138: 7244-7247
- PubMed: 27213829
- DOI: https://doi.org/10.1021/jacs.6b03437
- Primary Citation of Related Structures:
5EJ4, 5EJ5, 5EJ6, 5EJ7, 5EJ8, 5EJ9, 5EJA - PubMed Abstract:
Enamine is a well-known reactive intermediate mediating essential thiamine-dependent catalysis in central metabolic pathways. However, this intermediate is not found in the thiamine-dependent catalysis of the vitamin K biosynthetic enzyme MenD. Instead, an active tetrahedral post-decarboxylation intermediate is stably formed in the enzyme and was structurally determined at 1.34 Å resolution in crystal. This intermediate takes a unique conformation that allows only one proton between its tetrahedral reaction center and the exo-ring nitrogen atom of the aminopyrimidine moiety in the cofactor with a short distance of 3.0 Å. It is readily convertible to the final product of the enzymic reaction with a solvent-exchangeable proton at its reaction center. These results show that the thiamine-dependent enzyme utilizes a tetrahedral intermediate in a mechanism distinct from the enamine catalytic chemistry.
Organizational Affiliation:
Department of Chemistry, ‡State Key Laboratory for Molecular Neuroscience, and §Environmental Science Program, The Hong Kong University of Science and Technology , Clear Water Bay, Kowloon, Hong Kong SAR, China.
