The coordination tendencies of phosphorus to form a hexacoordinated state from a pentacoordinated state which might assist in describing mechanistic action of phosphoryl transfer enzymes are delineated. The factors discussed include substrate and transition or intermediate state anionicity; hydrogen bonding; packing effects, i.e., van der Waals forces; the ease of formation of hexacoordinate phosphorus from lower coordinate states; and the pseudorotation problem common to nonrigid pentacoordinate phosphorus. In view of the work reported in this account and recent work on enzyme promiscuity and moonlighting activities, it is suggested that donor action should play a role in determining active-site interactions in phosphoryl transfer enzyme mechanisms.
Reprinted in part with permission from Acc. Chem. Res., 2004, 37(10), 746–753. Copyright© 2004 American Chemical Society.
The research reviewed here was supported by the National Science Foundation and the donors of the Petroleum Research Fund, administered by the American Chemical Society, and the support is gratefully acknowledged.
The work summarized here formed the basis of the keynote lecture given by the author at the 7th International Conference on Heteroatom Chemistry (ICHAC-7) held in Shanghai, China, August 20–25, 2004.
The reference numbers cited in this article correspond to those listed in R. R. Holmes, Acc. Chem. Res., 37, 746–753, 2004. Work not cited therein is individually referenced in the text of this article.