Tryptophan synthase: the workings of a channeling nanomachine

Substrate channeling between enzymes has an important role in cellular metabolism by compartmentalizing cytoplasmic synthetic processes. The bacterial tryptophan synthases are multienzyme nanomachines that catalyze the last two steps in L−tryptophan biosynthesis. The common metabolite indole is transferred from one enzyme to the other in each αβ−dimeric unit of the α2β2 complex via an interconnecting 25−Å−long tunnel. Recent solution studies of the Salmonella typhimurium α2β2 complex coupled with X−ray crystal−structure determinations of complexes with substrates, intermediates and substrate analogs have driven important breakthroughs concerning the identification of the linkages between the bi−enzyme complex structure, catalysis at the α− and β−active sites, and the allosteric regulation of substrate channeling