Allosteric ACTion: the varied ACT domains regulating enzymes of amino-acid metabolism

•The ACT domain is a 60–70 residue domain with a topology.•The ACT domain is associated with the allosteric regulation of enzymes of amino-acid metabolism.•ACT domains interact forming oligomeric structures.•Fusion of the ACT domain to an unregulated enzyme can confer allostery. Allosteric regulation of enzyme activity plays important metabolic roles. Here we review the allostery of enzymes of amino-acid metabolism conferred by a discrete domain known as the ACT domain. This domain of 60–70 residues has a βαββαβ topology leading to a four-stranded β4β1β3β2 antiparallel sheet with two antiparallel helices on one face. Extensive sequence variation requires a combined sequence/structure/function analysis for identification of the ACT domain. Common features include highly varied modes of self-association of ACT domains, ligand binding at domain interfaces, and transmittal of allosteric signals through conformational changes and/or the manipulation of quaternary equilibria. A recent example illustrates the relatively facile adoption of this versatile module of allostery by gene fusion.