Phosphorus in Biology Why Nature Chose Phosphate

Suggest a mechanism and an HSAB rationale for the following ligand exchange (metathesis) reaction  

The term phosphorylation refers to the addition of phosphoryl groups to organic molecules, typically with ATP as the phosphoryl donor. Such reactions are catalyzed by a class of enzymes called kinases. The enzyme catalyzing the above reaction is called glucokinase. 

Kinases not only bind ATP and other phosphoryl donors but also enhance the electrophilic-ity of the migrating phosphate group by coordination with one or two Mg ions. The mechanism of phosphoryl transfer is essentially an 8 2 reaction, which we may represent as shown below (B is an active site base). For clarity, we have not included any of the Mg ions in our simplified picture  

Note that the mechanism, as indicated above, implies inversion of stereochemistry at the phosphorus. Proving that, however, was no simple matter because an ordinary phosphate group is not stereogenic. In 1978, in an experimental tour de force, Jeremy Knowles and coworkers at Harvard used and isotopes to create organic phosphates with stereogenic phosphate groups in enantiomerically enriched form. Subsequent experimental work confirmed inversion of stereochemistry in the product, providing support for the overall Sn2 nature of the process. 

Although the above remains the mechanistic paradigm for enzymatic phosphoryl transfer, other mechanistic variants have been uncovered since the original breakthroughs these, however, are outside the scope of our discussion. 

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