Donor interactions at phosphorus. Implications regarding enzymatic reaction intermediates

In recent work on the biological relevance of hypervalent phosphorus compou nds, a new aspect of active site interactions of phosphoryl transfer enzyme s undergoing nucleophilic attack is suggested by structural studies on phos phites, phosphates, and oxyphosphoranes which are shown to interact with do nor groups to give higher coordinate geometries. The degree of coordination increases from phosphate to pentaoxyphosphoranes which model substrates an d active site transition states, respectively. Thus a rate enhancement effe ct is anticipated due to stronger enzyme binding in the transition state-en zyme complex. The studies suggest that donor interactions at applicable act ive sites may assist in nucleophilic attack in causing a general loosening of P-O bonds undergoing cleavage to form products via a hexacoordinate tran sition state. Previously, only pentacoordinate intermediates have been invo ked in nucleophilic displacement reactions of phosphoryl transfer enzymes. The results are illustrated with reference to the tyrosyl-tRNA synthetase s ystem. Earlier, application to the enzymatic hydrolysis of cAMP was made.