Functional characterization of thioesterase superfamily member 1/Acyl-CoA thioesterase 11: implications for metabolic regulation

Structural Basis for Regulation of the Human Acetyl-CoA Thioesterase 12 and Interactions with the Steroidogenic Acute Regulatory Protein-related Lipid Transfer (START) Domain

“…This will prove to be a useful feature in the prediction of CoA binding sites in eukaryotic thioesterases. In similar fashion to the CoA binding site, the active site residues for ACOT12 also reside on the opposite domains to those for ACOT7, and comprised of D 36 and N 195 in ACOT12, equivalent to the ACOT7 active site (N 24 , D 213 ) (Fig. 2C) (34).…”

“…Significantly, the interaction between the thioesterase and START domains is distinct from the ADP-binding pocket, and therefore, it is unlikely that the START domain plays a role in regulation of the ACOT12 activity. Interestingly, START domain regulation has been reported by previous researchers for both ACOT12 (14) and ACOT11 (36), the mechanism of which is still unknown and will be the subject of future research.…”

Enzymatic and transcriptional regulation of the cytoplasmic acetyl-CoA hydrolase ACOT12

“…The thioesterase activity of ACOT11, known as thioesterase superfamily member 1 or StarD14, another hotdog-fold ACOT member with a C-terminal START domain, was recently characterized ( 29 ). This enzyme preferentially hydrolyzes long chain acyl-CoA compounds such as palmitoyl-CoA and myristoyl-CoA.…”

Deactivating Fatty Acids: Acyl-CoA Thioesterase-Mediated Control of Lipid Metabolism

“…This inclusion of a START-domain is an occurrence that is so far limited to mammalian ACOTs and is suggested to provide an additional level of intrinsic lipid-mediated regulation of the thioesterase activity [8, 23, 27, 30]. Interestingly, the single HotDog domain ACOT13 was originally identified as a binding partner of the minimal START domain protein phosphatidylcholine transfer protein (PC-TP; synonym StarD2) [31].…”

“…THEM1 hydrolyzes a broad range of substrates from acetyl-CoA to long chain fatty acyl-CoAs, with long chain acyl-CoAs being preferred in vitro [30, 51]. The lipid ligand of the START domain remains unknown, although the crystal structure suggests FFA may be accommodated within the lipid binding pocket [52].…”