A novel ligand-binding domain, named the 'ACT domain', was recently identified by a PSI-BLAST search. The archetypical ACT domain is the C-terminal regulatory domain of 3-phosphoglycerate dehydrogenase (3PGDH), which folds with a ferredoxin-like betaalphabetabetaalphabeta topology. A pair of ACT domains form an eight-stranded antiparallel sheet with two molecules of the allosteric inhibitor serine bound in the interface. The ACT domain is found in a variety of contexts and is proposed to be a conserved regulatory ligand binding fold. Rat phenylalanine hydroxylase has a regulatory domain with a similar fold, but different ligand-binding mode. Putative ACT domains in some proteins of unknown structure (e.g. acetohydroxyacid synthase regulatory subunits) may also fold like the 3PGDH regulatory domain. The regulatory domain of threonine deaminase, although not a member of the ACT sequence family, is similar in structure to the paired 3PGDH regulatory domains. Repeats of ACT-like domains can create nonequivalent ligand-binding sites with the potential for complex regulatory patterns. The structures and mechanisms of such systems have only begun to be examined.