MECHANISTIC STUDIES OF AN ANTIBODY WITH CHORISMATE MUTASE ACTIVITY

Abstract. Antibody lF7 catalyzes the rearrangement of chorismate to prephenate. Its kinetic parameters are unaffected by changes in pH and display no solvent isotope effect or effects from addition of various cationic salts. These results are consistent with high-resolution structural information of lF7 bound to a transition state analog. The conversion of (-)-chorismate 1 to prephenate 3 was one of the first nonhydrolytic reactions to be catalyzed by an antibody.1~2 Chorismate mutase accelerates this reaction 2 x 106-fold over background,3 and both the thermal and enzyme-catalyzed reactions are believed to be concerted pericyclic rearrangements with chairlike transition states (2).4*s The bicyclic compound 4 (Figure l), which mimics this conformationally constrained high energy species tate, is an excellent inhibitor of the enzyme’s and has been used as a template to induce antibodies with significant chorismate mutase activity. Iv2 One of these catalytic antibodies, lF7, accelerates the rate of rearrangement by200-fold with high enantioselectivity.1*7 2945 2946 J. A. SHIN and D. HtLvF.RT The three-dimensional structure of lF7 bound to the transition state analog 4 has recently been determined to 3.0 A resolution (Figure 1).8 The antibody’s structural properties accurately reflect those of th