Mechanism of Enzyme Inhibition by Phosphate Esters

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Science  11 Sep 1959:
Vol. 130, Issue 3376, pp. 625-626
DOI: 10.1126/science.130.3376.625


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.