24-Thiacycloartanol, a potent mechanism-based inactivator of plant sterol methyltransferase

The rationally designed substrate mimic of cycloartenol, 24-thiacycloartanol (24-TC) 4A, and its corresponding sulfonium salt 5A were tested against the recombinant sterol methyltransferase (SMT) from Glycine max (soybean). Analog 4A was found to irreversibly inactivate the enzyme generating competitive- and time-dependent inhibition of activity accompanied by a Ki value of 2 μM and kinact of 0.3 min−1. Analog 5A, a presumptive high-energy intermediate of the SMT catalyzed reaction, was found to be a reversible, non-competitive-type inhibitor generating a Ki value of 55 nM.