Convergence of Catalytic Antibody and Terpene Cyclase Mechanisms: Polyene Cyclization Directed by Carbocation-π Interactions

Abstract

A tandem cationic cyclization cascade similar to a terpenoid cyclase reaction is catalyzed by antibody HA5-19A4. The 2.7-Å resolution crystal structure of the Fab-hapten complex reveals convergence with the same catalytic strategy employed by a terpenoid cyclase: both serve as templates that enforce the productive conformation of a flexible polyene substrate, and both stabilize carbocation intermediates through cation-π interactions with multiple aromatic residues in their active sites.