InterPro domain: IPR016039

This superfamily represents a structural domain with a thiolase-like 3-layer alpha/beta/alpha topology. This domain usually occurs in two similar copies that are related by a pseudo-dyad, and which arose through duplication. The proteins in this entry can be split into two groups: those related to thiolase, and those related to chalcone synthase. The thiolase-like enzymes include:

• Thiolase, where the topology of each domain is similar to the first domain of phosphoglucomutase [ 1 ]
• Beta-ketoacyl-ACP synthases types I ( 2.3.1.41 ) and II ( 2.3.1.179 ) [ 2 , 3 ]
• Actinorhodin polyketide beta-ketoacyl synthases 1 and 2 [ 4 ]
• Fatty oxidation complex beta subunit (3-ketoacyl-CoA thiolase; 2.3.1.16 ) [ 5 ]

The chalcone synthase-like enzymes include:

• Chalcone synthase ( 2.3.1.74 ) [ 6 ]
• Ketoacyl-ACP synthase III (FabH; 2.3.1.180 ) [ 7 ]
• Polyketide synthases [ 8 ]
• 3-hydroxy-3-methylglutaryl CoA synthase ( 2.3.3.10 ) [ 9 ]
• Dihydropinosylvin synthase [ 10 ]

1. The 1.8 A crystal structure of the dimeric peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: implications for substrate binding and reaction mechanism. J. Mol. Biol. 273, 714-28
2. Fatty acid synthesis. Role of active site histidines and lysine in Cys-His-His-type beta-ketoacyl-acyl carrier protein synthases. FEBS J. 273, 695-710
3. Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes. EMBO J. 17, 1183-91
4. An antibiotic factory caught in action. Nat. Struct. Mol. Biol. 11, 888-93
5. Structural basis for channelling mechanism of a fatty acid beta-oxidation multienzyme complex. EMBO J. 23, 2745-54
6. Structure-guided programming of polyketide chain-length determination in chalcone synthase. Biochemistry 40, 14829-38
7. Refined structures of beta-ketoacyl-acyl carrier protein synthase III. J. Mol. Biol. 307, 341-56
8. A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites. Nat. Struct. Mol. Biol. 11, 894-900
9. Staphylococcus aureus 3-hydroxy-3-methylglutaryl-CoA synthase: crystal structure and mechanism. J. Biol. Chem. 279, 44883-8
10. An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases. Chem. Biol. 11, 1179-94