Substrate recognition by 'password' in p-hydroxybenzoate hydroxylase

The enzyme p-hydroxybenzoate hydroxylase (PHBH) has to bind an ionizable phenolic substrate so that the NADPH may effectively reduce the enzyme's flavin. In the presence of NADPH, ionization of the phenol constitutes a 'password' that allows movement of the flavin ring system toward the surface of the enzyme, where reduction takes place. The linkage of substrate deprotonation to flavin movement is a novel mode of molecular recognition in which the enzyme tests the suitability of aromatic substrates before committing to the catalytic cycle.