3-ketoacyl-CoA thiolase is part of a complex of enzymes that work together to catabolize fatty acids. The protein catalyzes the final step of the beta-oxidation cycle by reversibly splitting the 3-ketoacyl-CoA substrate into acetyl-CoA and acyl-CoA. The acyl-CoA product is reduced in length by 2 carbons and is free to enter another fatty acid beta-oxidation cycle. 3-ketoacyl-CoA thiolase is an alpha and beta protein with a thiolase-like fold. The entire enzyme complex composed of 3-ketoacyl-CoA thiolase, 2-Enoyl-CoA hydratase and L-3-Hydroxyacyl-CoA dehydrogenase has been crystallized from Pseudomonas fragi in complex with Acetyl CoA and NAD+ (1WDK). 3-ketoacyl-CoA thiolase from P. fragi has 61% identity and 1.1Å RMSD with the current Salmonella typhimurium structure. The part of the molecule that is in contact with 2-Enoyl-CoA hydratase in the enzyme complex forms an alpha-helix, but is completely disordered in this structure. Although Acetyl-CoA was added to the mother liquor, there is no ordered electron density for it and the catalytic triad of Cys91, Cys373, and His343 are only in contact with ordered water. Other structures of 3-ketoacyl-CoA thiolase include those from Thermus thermophilus (1ULQ), Homo sapiens (1WL4) and Zoogloea ramigera (1M1T).
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