Thioesterase: Difference between revisions

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{{STRUCTURE_1u8u|  PDB=1u8u  | SIZE=400| SCENE= |right|CAPTION=E. Coli Acyl-CoA thioesterase complex with octanoic acid, glycerol and sulfate [[1u8u]] }}
<StructureSection load='' size='350' side='right' caption='Human ubiquitin esterase 2 (deepskyblue) complex with ubiquitin (green) and zinc+2 ion (grey) (PDB code [[2hd5]]).' scene='48/489265/Cv/2'>
 
__TOC__
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== Function ==
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'''Thioesterase''' (TE) catalyzes the break of an ester bond to produce acid and alcohol at a thiol group.  TEs are substrate-specific.<br />
'''Thioesterase''' (TE) catalyzes the break of an ester bond to produce acid and alcohol at a thiol group.  TEs are substrate-specific.<br />
*  '''Palmitoyl protein TE''' removes fatty acids like palmitate from modified cysteine residues during lysosomal degradation.<br />
*  '''Palmitoyl protein TE''' removes fatty acids like palmitate from modified cysteine residues during lysosomal degradation<ref>PMID:10737604</ref>.  For details see [[Palmitoyl protein thioesterase]].<br />
*  '''4-hydroxybenzoyl-CoA TE''' converts 4-hydroxybenzoyl-CoA to 4-hydroxybenzoate and CoA.<br />
*  '''4-hydroxybenzoyl-CoA TE''' converts 4-hydroxybenzoyl-CoA to 4-hydroxybenzoate and CoA<ref>PMID:12732540</ref>.<br />
*  '''Acyl-CoA TE''' hydrolyzes acyl-CoA to the fatty acid and CoA and is involved in lipid metabolism.<br />
*  '''Acyl-CoA TE''' hydrolyzes acyl-CoA to the fatty acid and CoA and is involved in lipid metabolism<ref>PMID:11755680</ref>.  See also [[YbgC]] and [[Mitochondrial hotdog-fold thioesterase]].<br />
*  '''Fluoroacetyl-CoA TE''' from ''Streptomyces cattleya'' hydrolyzes fluoroacetyl-CoA thus preventing it from being metabolized to the lethal 4-hydroxy-trans-aconitate.<br />
*  '''Fluoroacetyl-CoA TE''' from ''Streptomyces cattleya'' hydrolyzes fluoroacetyl-CoA thus preventing it from being metabolized to the lethal 4-hydroxy-trans-aconitate<ref>PMID:20836570</ref>.<br />
*  '''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 (UB).  The USPs are involved in the processing of poly-UB precursors and of ubiquinated proteins.  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.  
*  '''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<ref>PMID:24190967</ref>.  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.<br />
* '''USP-L1, USP25''' hydrolyze C-terminal adducts of UB.<br />
* USP-L3 hydrolyze C-terminal adducts of UB and NEDD8.<br />
* '''USP-L3''' hydrolyzes C-terminal adducts of UB and NEDD8.<br />
* USP5 cleaves multiubiquitin polymers.<br />
* '''USP5''' cleaves multiubiquitin polymers.<br />
* USP6 has ATP-independent isopeptidase activity.<br />
* '''USP6''' has ATP-independent isopeptidase activity.<br />
* USP7, USP4, USP13, USP15 deubiquitinate several proteins.<br />
* '''USP7, USP4, USP13, USP15''' deubiquitinate several proteins.<br />
* 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.<br />
* '''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.<br />
* USP11, USP14 are proteasome-associated.<br />
* '''USP11, USP14''' are proteasome-associated.<br />
* USP16, USP21 deubiquitinate histone H2A.<br />
* '''USP12''' stabilizes T-cell complexes<ref>PMID:26811477</ref>.<br />
* USP28 deubiquitinates proteins of the DNA damage pathway.<br />
* '''USP16, USP21''' deubiquitinate histone H2A.<br />
* USP33 regulates centrosome duplication.<br />
* '''USP18''' is a down regulator of the type I interferon signaling pathway<ref>PMID:23700969</ref>.<br />
* USP37 deubiquitinates cyclin A.<br />
* '''USP28''' deubiquitinates proteins of the DNA damage pathway.<br />
* '''USP33''' regulates centrosome duplication.<br />
* '''USP37''' deubiquitinates cyclin A.<br />
* '''USP46''' deubiquitinates AMPA receptor<ref>PMID:26077708</ref>.<br />


== Disease ==
Mutations in palmiotoyl protein TE cause neuronal ceroid lipocfuscinosis<ref>PMID:7637805</ref><ref>PMID:11506414</ref>.


== Structural highlights ==
<scene name='48/489265/Cv/7'>Human ubiquitin esterase 2 complex with ubiquitin and zinc+2 ion</scene>. Ubiquitin thioesterase 2 active site contains the <scene name='48/489265/Cv/8'>catalytic triad Cys-His-Asn and the oxyanion hole Asn</scene>. The metal-binding enzyme contains a <scene name='48/489265/Cv/9'>Zn+2 ion which coordinates to 4 Cys residues</scene>. The <scene name='48/489265/Cv/10'>ubiquitin coordinates to the thioesterase via residues in all thioesterase domains: finger, palm and thumb</scene><ref>PMID:16905103</ref>.
==3D structures of thioesterase==
==3D structures of thioesterase==
[[Thioesterase 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
 
===Maristoyl-ACP-specific TE===
 
[[1tht]] – TE – Vibrio harveyi
 
===4-hydroxybenzoyl-CoA TE===
 
[[1bvq]] – PsTE – ''Pseudomonas''<br />
[[1lo7]] – PsTE + 4-hydroxyphenyl CoA<br />
[[1lo9]] - PsTE (mutant) + 4-hydroxybenzoyl CoA<br />
[[1lo8]] - PsTE + 4-hydroxybenzyl CoA<br />
[[1q4s]] - ArTE + 4-hydroxybenzoate – '''Arthrobacte''r'<br />
[[1q4t]] - ArTE + 4-hydroxyphenyl CoA<br />
[[1q4u]] - ArTE + 4-hydroxybenzyl CoA<br />
[[3r32]], [[3r35]], [[3r37]], [[3r38]], [[3r3b]], [[3r3c]], [[3r3d]], [[3r3f]], [[3tea]] - ArTE (mutant) + 4-hydroxyphenacyl CoA<br />
[[3r36]] - ArTE (mutant) + 4-hydroxybenzoate<br />
[[3r3a]] - ArTE (mutant) + 4-hydroxybenzoate + CoA<br />
[[3r34]] - ArTE (mutant) + CoA<br />
 
===Palmitoyl protein TE===
 
[[1eh5]] – bTE1 + Palmitate – bovine<br />
[[1ei9]] – bTE1<br />
[[1exw]] – bTE1 + hexadecylsulfonyl fluoride<br />
[[1pja]] – hTEII – human<br />
[[3gro]] - hTEI
 
===Acyl-CoA TE===
 
[[1c8u]] – EcTEII – ''Escherichia coli''<br />
[[1ivn]] – EcTEI<br />
[[1jrl]] – EcTEI (mutant) <br />
[[1j00]] – EcTEI + diethyl phosphono derivative<br />
[[1v2g]], [[1u8u]] - EcTEI + octanoic acid<br />
[[2v1o]] – mTE7 hotdog domain – mouse<br />
[[2q2b]] – mTE7 C terminal<br />
[[3hlk]] – hTE2<br />
[[3k2i]] – hTE4<br />
[[2qq2]] - hTE7 C terminal<br />
[[3fo5]] – hTE11 START domain<br />
[[3b7k]] – hTE12<br />
[[3rd7]] – TE – ''Mycobacterium avium''<br />
[[3u0a]] – TEII – ''Mycobacterium marinum''<br />
[[1tbu]] – TE N terminal (peroximal) – yeast
 
===Acyl protein TE===
 
[[1fj2]] – EcTEI
 
===Acyl-ACP TE===
 
[[2ess]] – TE – ''Bacterioides thetaiotaomicron''<br />
[[4gak]] – TE – ''Spirosoma linguale''<br />
[[4gwh]] – TE – ''Yersinia pestis''<br />
 
===ACP-polyene TE===
 
[[4i4j]] – TE – ''Streptomyces globisporus''<br />
 
===Fluoroacetyl-CoA TE===
 
[[3kuv]], [[3kuw]], [[3kvi]] – ScTE (mutant) + acetate derivative – ''Streptomyces cattleya''<br />
[[3kv7]], [[3kv8]], [[3p2r]], [[3p2s]] – ScTE + acetate derivative<br />
[[3kvu]] – ScTE + acetyl-CoA<br />
[[3kvz]], [[3kw1]] – ScTE + FAcOPan<br />
[[3kx7]], [[3kx8]], [[3p2q]] – ScTE <br />
[[3p3f]] – ScTE (mutant) <br />
[[3p3i]] - ScTE (mutant) + acetate derivative + CoA<br />
 
===DHNA-CoA TE===
 
[[4k00]] – TE – ''Synechocystis''<br />
[[4k02]] – TE – ''Arabidopsis thaliana''<br />
 
===Ubiquitin TE===
 
''USP 2''
 
[[2zfy]] – hUSP – human  <BR />
[[2hd5]], [[3nhe]], [[3v6c]], [[3v6e]] – hUSP + Ub  <BR />
[[1tff]] – hUSP (mutant)  <BR />
[[2ibi]] – hUSP (mutant) + Ub <BR />
 
''USP 3''
 
[[2qiy]] – yUSP + USP-associated protein – yeast  <BR />
 
''USP 4''
 
[[2y6e]] – hUSP catalytic domain <br />
[[3jyu]] – mUSP N terminal domain - mouse<br />
 
''USP 5''
 
[[2dag]] – hUSP UBA domain 1 - NMR<br />
[[2dak]] – hUSP UBA domain 2 - NMR<br />
[[2g43]] – hUSP zinc finger USP domain<br />
[[2g45]] – hUSP zinc finger USP domain + Ub<br />
[[3ihp]] – hUSP + Ub  <BR />
 
''USP 7''
 
[[2f1z]] – hUSP<br />
[[1nb8]], [[4m5w]], [[4m5x]] – hUSP catalytic domain <br />
[[2kvr]] – hUSP UBL domain - NMR<br />
[[4pyz]] – hUSP UBL domains 1+2<br />
[[1yze]], [[2f1w]] – hUSP N terminal domain <br />
[[2ylm]] – hUSP C terminal domain <br />
[[2f1x]], [[2f1y]], [[2foj]], [[2foo]], [[2fop]] – hUSP N terminal domain/peptide <br />
 
''USP 7 complexes''
 
[[1nbf]] – hUSP catalytic domain + Ub aldehyde<br />
[[1yy6]] – hUSP N terminal domain + EBNA1 peptide<br />
[[2xxn]] – hUSP TRAF domain + VIRF-4 peptide<br />
[[3mqr]] – hUSP TRAF domain + HDMX peptide<br />
[[3mqs]] – hUSP TRAF domain + HDM2 peptide<br />
[[4jjq]] – hUSP TRAF domain + E2 peptide<br />
[[4kg9]] – hUSP TRAF domain + MCM-BP peptide<br />
 
''USP 8''
 
[[1whb]] – hUSP rhodanase domain – human - NMR<br />
[[2a9u]] – hUSP N terminal domain <br />
[[2gfo]] – hUSP catalytic domain <br />
 
''USP 8 complexes''
 
[[2gwf]] – hUSP rhodanase domain + ring finger protein 41 USP8 interaction domain<br />
[[3mhh]], [[3m99]], [[4fip]], [[4fjc]], [[4f5k]], [[4fk5]] – yUSP + SUS1 + SGF11 +SGF73 <br />
[[3mhs]] – yUSP + SUS1 + SGF11 +SGF73 + Ub<br />
[[3n3k]] – hUSP catalytic domain + Ub<br />
 
''USP 11''
 
[[4mel]] – hUSP DUSP+UBL domains <br />
[[4mem]] – rUSP DUSP+UBL domains - rat<br />
 
''USP 13''
 
[[2l80]] – hUSP zinc finger domain - NMR<br />
[[2lbc]] – hUSP UBA domain - NMR<br />
 
''USP 14''
 
[[1wgg]] – mUSP N terminal domain - NMR<br />
[[2ayn]] – hUSP<br />
[[2ayo]] – hUSP + Ub aldehyde<br />
 
''USP 15''
 
[[3lmn]] – hUSP DUSP domain  <BR />
[[3ppa]], [[3pv1]], [[3t9l]], [[4a3o]], [[4a3p]] – hUSP DUSP+UBL domains <br />
[[1w6v]] – hUSP DUSP domain - NMR<br />
 
''USP 16''
 
[[2i50]] – hUSP zinc finger domain - NMR  <BR />
 
''USP 21''
 
[[3i3t]], [[2y5b]] – hUSP + Ub  <BR />
[[3mtn]] – hUSP + Ub inhibitor <BR />
 
''USP25''
 
[[1vdl]] – mUSP catalytic domain <br />
 
''USP 28''
 
[[2lva]] – hUSP N terminal - NMR  <BR />
 
''USP 33''
 
[[2uzg]] – hUSP zinc finger domain - NMR  <BR />
 
''USP 37''
 
[[3ihr]] – hUSP (mutant)  <BR />
[[3a7s]] – hUSP catalytic domain (mutant)  <BR />
 
''USP Cyld''
 
[[2vhf]] – hUSP  USP domain <BR />
 
''USP L1''
 
[[2etl]] – hUSP-L1  <br />
[[3irt]], [[4jkj]] – hUSP  (mutant) <BR />
[[2len]] – hUSP  (mutant) - NMR<BR />
[[3ifw]], [[3kvf]], [[3kw5]] – hUSP  (mutant) + Ub<BR />
[[4dm9]] – hUSP + peptide inhibitor<BR />
 
''USP L3''
 
[[1uch]] – hUSP-L3  <br />
[[1xd3]] – hUSP-L3 + UBC<br />
[[2we6]] – PfUSP-L3 – ''Plasmodium falciparum''<br />
[[2wdt]] – PfUSP-L3 + Ub <br />
 
''USP L5''
 
[[3ris]] – hUSP catalytic domain  <BR />
[[3rii]], [[3a7s]] – hUSP catalytic domain (mutant)  <BR />
[[3tb3]] – hUSP UCH domain (mutant)  <BR />
[[3ihr]] – hUSP-L5 (mutant)  <br />
 
''USP ZranB1''
 
[[3zrh]] – hUSP  <BR />
 
''USP OTUB1''
 
[[3von]] – hUSP + E2 <BR />
[[4ddg]], [[4ddi]] – hUSP + Ub<BR />
[[4ddi]], [[4i6l]] – hUSP (mutant) + Ub<BR />
[[4dhz]] – hUSP + E2 + Ub<BR />
[[4boq]] - hUSP OTU domain <BR />
[[4boz]] - hUSP OTU domain (mutant) + Ub <BR />
[[4bos]] - hUSP OTU domain (mutant) + Ub + OTUD2 peptide<BR />
[[4fjv]] - hUSP OTUB2 + Ub <BR />
[[4dhj]] – nUSP + E2 + Ub - nematode<BR />
[[4dhi]] – nUSP + E2 <BR />
[[2kzr]] – mUSP UBX-like domain – NMR<br />
[[4kdi]], [[4kdl]] – yUSP UBX-like domain + transitional endoplasmic reticulum ATPase<br />
[[3by4]], [[3c0r]] - yUSP OTU domain + Ub<BR />
 
[[3znh]] – USP + Ub – Crimean-Congo hemorrhagic fever virus<BR />
 
===RedJ TE===
 
[[3qmv]], [[3qmw]] – TE –'' Streptomyces coelicolor''
 
===Orf6 TE===
 
[[4i45]] – TE – ''Photobacterium profundum''<br />
 
[[2av9]], [[2o5u]], [[2o6b]], [[2o6t]], [[2o6u]], [[3qy3]] – TE – ''Pseudomonas aeruginosa''


== References ==
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

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Michal Harel, Alexander Berchansky, Joel L. Sussman
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