Structures of fungal and plant acetohydroxyacid synthases.

Acetohydroxyacid synthase (AHAS), also known as acetolactate synthase, is a FAD and ThDP-Mg2+-dependent enzyme that catalyses the first step in the biosynthesis of the branched chain amino acids (BCAAs)1. It is the target for over 50 commercial herbicides2. AHAS requires both catalytic and regulatory subunits for maximal activity and functionality. Herein, our structures of the hexadecameric Saccharomyces cerevisiae and dodecameric Arabidopsis thaliana AHAS complexes demonstrate that the regulatory subunits form a core upon which the catalytic subunit dimers are attached, adopting the shape of a “Maltese Cross”. The structures show how the catalytic and regulatory subunits communicate with each other to provide a pathway for activation and for feedback inhibition by the BCAAs. We also show that Mycobacterium tuberculosis AHAS adopts a similar structure, thus demonstrating that the overall AHAS architecture is conserved across kingdoms.