ABSTRACT
The product of the first active site is transferred to the second active site of enzyme through tunnel and becomes the substrate of the second active site. The product iminium intermediate is easily transferred across the barrier, since the region is under dynamic motion in the reduced form. Tryptophan (Trp) is an essential amino acid in human, and tryptophan synthase (TRPS) catalyzes the last two reactions of Trp synthesis in bacteria, yeasts, molds, and plants. The pyridine nitrogen of PLP in the most PLP-dependent enzymes is protonated, but that of TRPS is unprotonated. Structural and rapid reaction kinetic analyses of the TRPS-catalyzed reactions revealed the following to be important for the catalysis and their communications. CAVER orders the tunnels based on ligand accessibility, that is, the tunnels that supply better access for ligands appear earlier.
