Proteopedia

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 and Mitochondrial hotdog-fold thioesterase.
  • 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); TRAF homology domain.
  • USP-L1, USP25 hydrolyze C-terminal adducts of UB.
  • USP-L3 hydrolyzes 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.
  • USP12 stabilizes T-cell complexes[6].
  • USP16, USP21 deubiquitinate histone H2A.
  • USP18 is a down regulator of the type I interferon signaling pathway[7].
  • USP28 deubiquitinates proteins of the DNA damage pathway.
  • USP33 regulates centrosome duplication.
  • USP37 deubiquitinates cyclin A.
  • USP46 deubiquitinates AMPA receptor[8].

Disease

Mutations in palmiotoyl protein TE cause neuronal ceroid lipocfuscinosis[9][10].

Structural highlights

. Ubiquitin thioesterase 2 active site contains the . The metal-binding enzyme contains a . The [11].

3D structures of thioesterase

Thioesterase 3D structures


Human ubiquitin esterase 2 (deepskyblue) complex with ubiquitin (green) and zinc+2 ion (grey) (PDB code 2hd5).

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Cho S, Dawson G. Palmitoyl protein thioesterase 1 protects against apoptosis mediated by Ras-Akt-caspase pathway in neuroblastoma cells. J Neurochem. 2000 Apr;74(4):1478-88. PMID:10737604
  2. ↑ Zhuang Z, Gartemann KH, Eichenlaub R, Dunaway-Mariano D. Characterization of the 4-hydroxybenzoyl-coenzyme A thioesterase from Arthrobacter sp. strain SU. Appl Environ Microbiol. 2003 May;69(5):2707-11. PMID:12732540
  3. ↑ Hunt MC, Alexson SE. The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Prog Lipid Res. 2002 Mar;41(2):99-130. PMID:11755680
  4. ↑ Weeks AM, Coyle SM, Jinek M, Doudna JA, Chang MC. Structural and Biochemical Studies of a Fluoroacetyl-CoA-Specific Thioesterase Reveal a Molecular Basis for Fluorine Selectivity. Biochemistry. 2010 Oct 11. PMID:20836570 doi:10.1021/bi101102u
  5. ↑ Jagannathan M, Nguyen T, Gallo D, Luthra N, Brown GW, Saridakis V, Frappier L. A role for USP7 in DNA replication. Mol Cell Biol. 2014 Jan;34(1):132-45. doi: 10.1128/MCB.00639-13. Epub 2013 Nov 4. PMID:24190967 doi:http://dx.doi.org/10.1128/MCB.00639-13
  6. ↑ Jahan AS, Lestra M, Swee LK, Fan Y, Lamers MM, Tafesse FG, Theile CS, Spooner E, Bruzzone R, Ploegh HL, Sanyal S. Usp12 stabilizes the T-cell receptor complex at the cell surface during signaling. Proc Natl Acad Sci U S A. 2016 Feb 9;113(6):E705-14. doi:, 10.1073/pnas.1521763113. Epub 2016 Jan 25. PMID:26811477 doi:http://dx.doi.org/10.1073/pnas.1521763113
  7. ↑ Malhotra S, Morcillo-Suarez C, Nurtdinov R, Rio J, Sarro E, Moreno M, Castillo J, Navarro A, Montalban X, Comabella M. Roles of the ubiquitin peptidase USP18 in multiple sclerosis and the response to interferon-beta treatment. Eur J Neurol. 2013 Oct;20(10):1390-7. doi: 10.1111/ene.12193. Epub 2013 May 22. PMID:23700969 doi:http://dx.doi.org/10.1111/ene.12193
  8. ↑ Huo Y, Khatri N, Hou Q, Gilbert J, Wang G, Man HY. The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking. J Neurochem. 2015 Sep;134(6):1067-80. doi: 10.1111/jnc.13194. Epub 2015 Jul 16. PMID:26077708 doi:http://dx.doi.org/10.1111/jnc.13194
  9. ↑ Vesa J, Hellsten E, Verkruyse LA, Camp LA, Rapola J, Santavuori P, Hofmann SL, Peltonen L. Mutations in the palmitoyl protein thioesterase gene causing infantile neuronal ceroid lipofuscinosis. Nature. 1995 Aug 17;376(6541):584-7. PMID:7637805 doi:http://dx.doi.org/10.1038/376584a0
  10. ↑ van Diggelen OP, Thobois S, Tilikete C, Zabot MT, Keulemans JL, van Bunderen PA, Taschner PE, Losekoot M, Voznyi YV. Adult neuronal ceroid lipofuscinosis with palmitoyl-protein thioesterase deficiency: first adult-onset patients of a childhood disease. Ann Neurol. 2001 Aug;50(2):269-72. PMID:11506414
  11. ↑ Renatus M, Parrado SG, D'Arcy A, Eidhoff U, Gerhartz B, Hassiepen U, Pierrat B, Riedl R, Vinzenz D, Worpenberg S, Kroemer M. Structural basis of ubiquitin recognition by the deubiquitinating protease USP2. Structure. 2006 Aug;14(8):1293-302. PMID:16905103 doi:10.1016/j.str.2006.06.012

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