Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex

The tryptophan synthase alpha(2)beta(2) bi-enzyme complex catalyzes the last two steps in the synthesis of L-tryptophan (L-Trp). The alpha-subunit catalyzes cleavage of 3-indole-D-glycerol 3'-phosphate (IGP) to give indole and D-glyceraldehyde 3'-phosphate (G3P). Indole is then transferred (channeled) via an interconnecting 25 A-long tunnel, from the alpha-subunit to the beta-subunit where it reacts with L-Ser in a pyridoxal 5'-phosphate-dependent reaction to give L-Trp and a water molecule. The efficient utilization of IGP and L-Ser by tryptophan synthase to synthesize L-Trp utilizes a system of allosteric interactions that (1) function to switch the alpha-site on and off at different stages of the beta-subunit catalytic cycle, and (2) prevent the escape of the channeled intermediate, indole, from the confines of the alpha- and beta-catalytic sites and the interconnecting tunnel. This review discusses in detail the chemical origins of the allosteric interactions responsible both for switching the alpha-site on and off, and for triggering the conformational changes between open and closed states which prevent the escape of indole from the bienzyme complex. (C) 2012 Elsevier Inc. All rights reserved.