Mechanism of enzyme inhibition by phosphate esters.

A theory for the rapid specific reaction of certain phosphorous-containing esters with many proteolytic enzymes based on the ability of phosphorous to form one additional bond relative to carbon is presented. A stable tetrahedral phosphate ester is compared with a labile tetrahedral orthocarbonyl ester and a relatively stable pentagonal enzyme-phosphate ester complex is compared with a pentagonal enzyme-carbonyl substrate complex. The latter complex is assumed to be the transition state in the enzyme-catalyzed reaction. If the theory is correct, it opens up the possibility of studying intermediates and transition states from the known structures of chemical inhibitors.