Allosteric regulation of substrate channeling and catalysis in the tryptophan synthase bienzyme complex.
The tryptophan synthase α2β2 bi-enzyme complex catalyzes the last two steps in the synthesis of l-tryptophan (l-Trp). The α-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 25Å-long tunnel, from the α-subunit to the β-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 α-site on and off at different stages of the β-subunit catalytic cycle, and (2) prevent the escape of the channeled intermediate, indole, from the confines of the α- and β-catalytic sites and the interconnecting tunnel. This review discusses in detail the chemical origins of the allosteric interactions responsible both for switching the α-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.
Department of Biochemistry, University of California at Riverside, Riverside, CA 92521, USA. michael.dunn@ucr.edu
Michael F
MF
Dunn
D000494:Allosteric Regulation; D055162:Biocatalysis; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D014367:Tryptophan Synthase / Q000737:chemistry* / Q000378:metabolism*
D014367:Tryptophan Synthase