Thioesterase

Function

Thioesterase (TE) catalyzes the break of an ester bond to produce acid and alcohol at a thiol group. TEs are substrate-specific.

• Palmitoyl protein TE removes fatty acids like palmitate from modified cysteine residues during lysosomal degradation^[1]. For details see Palmitoyl protein thioesterase.
  
• 4-hydroxybenzoyl-CoA TE converts 4-hydroxybenzoyl-CoA to 4-hydroxybenzoate and CoA^[2].
  
• Acyl-CoA TE hydrolyzes acyl-CoA to the fatty acid and CoA and is involved in lipid metabolism^[3]. See also YbgC.
  
• Fluoroacetyl-CoA TE from Streptomyces cattleya hydrolyzes fluoroacetyl-CoA thus preventing it from being metabolized to the lethal 4-hydroxy-trans-aconitate^[4].
  
• Ubiquitin TE or ubiquitin carboxyl-terminal hydrolase (USP) removes conjugated ubiquitin (UB) from proteins thus regulating protein level by preventing their degradation. USP hydrolyze the peptide bond at the C-terminal glycine of ubiquitin. The USPs are involved in the processing of poly-UB precursors and of ubiquitinated proteins^[5]. USP contains catalytic domain surrounded several domains: Ub-like (UBL); Ub-associated (UBA); zinc finger-Ub-specific protease domain (UBP or DUSP); TRF homology domain.

• USP-L1, USP25 hydrolyze C-terminal adducts of UB.
  
• USP-L3 hydrolyze C-terminal adducts of UB and NEDD8.
  
• USP5 cleaves multiubiquitin polymers.
  
• USP6 has ATP-independent isopeptidase activity.
  
• USP7, USP4, USP13, USP15 deubiquitinate several proteins.
  
• USP8 removes conjugated ubiquitin from proteins thus preventing protein degradation. USP8 is involved in cell proliferation and is active in the M phase of proliferation.
  
• USP11, USP14 are proteasome-associated.
  
• USP16, USP21 deubiquitinate histone H2A.
  
• USP28 deubiquitinates proteins of the DNA damage pathway.
  
• USP33 regulates centrosome duplication.
  
• USP37 deubiquitinates cyclin A.
  

Disease

Mutations in palmiotoyl protein TE cause neuronal ceroid lipocfuscinosis^[6][7].

Structural highlights

Ubiquitin thioesterase 2 active site contains the catalytic triad Cys-His-Asn and the oxyanion hole Asn. The metal-binding enzyme contains a Zn+2 ion which coordinates to 4 Cys residues. The ubiquitin coordinates to the thioesterase via residues in all thioesterase domains: finger, palm and thumb^[8].