Influence of multiple cysteines on human 3-hydroxy-3-methylglutaryl-CoA lyase activity and formation of inter-subunit adducts

► Stimulation of HMG-CoA lyase activity by reducing agents. ► Inter-subunit adduct formation in HMG-CoA lyase. ► Specific Cys → Ser mutations eliminate inter-subunit adducts in HMG-CoA lyase. ► HMGCL C266S/C323S heterodimer forms an inter-subunit adduct. ► Restoration of inter-subunit adducts in a double Cys → Ser HMG-CoA lyase mutant.