Fatty acid synthase thioesterase domain (FAS TE domain)

The fatty acid synthase thioesterase domain is the carboxyl-terminal catalytic domain of mammalian fatty acid synthase, a large multifunctional enzyme complex essential for the de novo biosynthesis of long-chain saturated fatty acids, most notably palmitic acid. The thioesterase domain hydrolyzes the thioester bond between the synthesized fatty acid and the acyl carrier protein domain, determining the release and chain length of the final fatty acid product—typically palmitate (C16:0). Structurally, it is comprised of two subdomains: one with a variation of the α/β hydrolase fold and a small all α-helical domain, creating a substrate binding groove that confers selectivity for long fatty acid chains. Overexpression of the fatty acid synthase and its thioesterase domain has been implicated in several human cancers and its inhibition reduces cancer cell viability, making it a promising drug target. Inhibitors, including certain polyunsaturated fatty acids, bind to and suppress the thioesterase activity, blocking the release of palmitate and inducing metabolic stress in cancer cells.

Other names

Fatty acid synthase thioesteraseFAS thioesterase domainFAS TE domainThioesterase domain of fatty acid synthase

Inhibitors typically block hydrolysis or alter substrate binding by interacting directly with the TE domain active site, often at the catalytic serine residue Some inhibitors induce loss of fatty acid chain release, affecting lipid synthesis and cell viability, especially in cancer cells