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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__ |
| | == Function == |
| | '''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<ref>PMID:10737604</ref>. For details see [[Palmitoyl protein thioesterase]].<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<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<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. 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. |
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| <!--
| | * '''USP-L1, USP25''' hydrolyze C-terminal adducts of UB.<br /> |
| Please use the "3D" button above this box to insert a Jmol applet (molecule) on this page.
| | * '''USP-L3''' hydrolyzes C-terminal adducts of UB and NEDD8.<br /> |
| Or use the four-green-boxes-button to insert scrollable text adjacent
| | * '''USP5''' cleaves multiubiquitin polymers.<br /> |
| to a Jmol applet. Check out the other buttons as well!
| | * '''USP6''' has ATP-independent isopeptidase activity.<br /> |
| --> | | * '''USP7, USP4, USP13, USP15''' deubiquitinate several proteins.<br /> |
| '''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. '''4-hydroxybenzoyl-CoA TE''' converts 4-hydroxybenzoyl-CoA to 4-hydroxybenzoate and CoA. '''Acyl-CoA TE''' hydrolyzes acyl-CoA to the fatty acid and CoA and is involved in lipid metabolism. '''Fluoroacetyl-CoA TE''' from ''Streptomyces cattleya'' hydrolyzes fluoroacetyl-CoA thus preventing it from being metabolized to the lethal 4-hydroxy-trans-aconitate. '''Ubiquitin TE''' (USP) removes conjugated ubiquitin from proteins thus regulating protein level by preventing their degradation. | | * '''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 /> |
| | * '''USP12''' stabilizes T-cell complexes<ref>PMID:26811477</ref>.<br /> |
| | * '''USP16, USP21''' deubiquitinate histone H2A.<br /> |
| | * '''USP18''' is a down regulator of the type I interferon signaling pathway<ref>PMID:23700969</ref>.<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 /> |
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| | == 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]] |
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
| | </StructureSection> |
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| '''Maristoyl-ACP-specific TE'''
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| [[1tht]] – TE – Vibrio harveyi
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| '''4-hydroxybenzoyl-CoA TE'''
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| [[1bvq]] – PsTE – ''Pseudomonas''<br />
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| [[1lo7]] – PsTE + 4-hydroxyphenyl CoA<br />
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| [[1lo9]] - PsTE (mutant) + 4-hydroxybenzoyl CoA<br />
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| [[1lo8]] - PsTE + 4-hydroxybenzyl CoA<br />
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| [[1q4s]] - ArTE + 4-hydroxybenzoate – '''Arthrobacte''r'<br />
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| [[1q4t]] - ArTE + 4-hydroxyphenyl CoA<br />
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| [[1q4u]] - ArTE + 4-hydroxybenzyl CoA<br />
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| [[3r32]], [[3r35]], [[3r37]], [[3r38]], [[3r3c]], [[3r3d]], [[3r3f]] - ArTE (mutant) + 4-hydroxyphenacyl CoA<br />
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| [[3r3a]] - ArTE (mutant) + 4-hydroxybenzoate<br />
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| [[3r34]] - ArTE (mutant) + CoA<br />
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| '''Palmitoyl protein TE'''
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| [[1eh5]] – bTE1 + Palmitate – bovine<br />
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| [[1ei9]] – bTE1<br />
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| [[1exw]] – bTE1 + hexadecylsulfonyl fluoride<br />
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| [[1pja]] – hTEII – human<br />
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| [[3gro]] - hTEI
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| '''Acyl-CoA TE'''
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| [[1c8u]] – EcTEII – ''Escherichia coli''<br />
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| [[1ivn]] – EcTEI<br />
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| [[1jrl]] – EcTEI (mutant) <br />
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| [[1j00]] – EcTEI + diethyl phosphono derivative<br />
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| [[1v2g]], [[1u8u]] - EcTEI + octanoic acid<br />
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| [[2v1o]] – mTE7 hotdog domain – mouse<br />
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| [[2q2b]] – mTE7 C terminal<br />
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| [[3hlk]] – hTE2<br />
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| [[3k2i]] – hTE4<br />
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| [[2qq2]] - hTE7 C terminal<br />
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| [[3fo5]] – hTE11 START domain<br />
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| [[3b7k]] – hTE12<br />
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| [[3rd7]] – TE – ''Mycobacterium avium''<br />
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| [[3u0a]] – TEII – ''Mycobacterium marinum''<br />
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| [[1tbu]] – TE N terminal (peroximal) – yeast
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| '''Acyl protein TE'''
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| [[1fj2]] – EcTEI
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| '''Acyl-ACP TE'''
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| [[2ess]] – TE – ''Bacterioides thetaiotaomicron''
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| '''Fluoroacetyl-CoA TE'''
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| [[3kuv]], [[3kuw]], [[3kvi]] – ScTE (mutant) + acetate derivative – ''Streptomyces cattleya''<br />
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| [[3kv7]], [[3kv8]], [[3p2r]], [[3p2s]] – ScTE + acetate derivative<br />
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| [[3kvu]] – ScTE + acetyl-CoA<br />
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| [[3kvz]] – ScTE + FAcOPan<br />
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| [[3kx7]], [[3fx8]], [[3p2q]] – ScTE <br />
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| [[3p3f]] – ScTE (mutant) <br />
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| [[3p3i]] - ScTE (mutant) + acetate derivative + CoA<br />
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| '''Ubiquitin TE'''
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| ''USP 2''
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| [[2zfy]] – hUSP – human <BR />
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| [[2hd5]], [[3nhe]] – hUSP + Ub <BR />
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| [[1tff]] – hUSP (mutant) <BR />
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| [[2ibi]] – hUSP (mutant) + Ub <BR />
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| ''USP 3''
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| [[2qiy]] – USP + UBP-associated protein – yeast <BR />
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| ''USP 5''
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| [[3ihp]] – hUSP + Ub <BR />
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| ''USP 7''
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| [[2ylm]] – hUSP <BR />
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| [[2kvr]] – hUSP UBL domain - NMR <BR />
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| [[3mqr]], [[3mqs]] – hUSP + peptide <BR />
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| [[2xxn]] – hUSP + VIRF-4 <BR />
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| [[4jjq]] – hUSP (mutant) + E2<BR />
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| ''USP 8''
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| [[2gwf]] – hUSP rhodanese domain + ring finger protein <BR />
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| [[3mhh]], [[3m99]], [[4fip]], [[4fjc]], [[4fk5]] – hUSP + SUS1 + SAGA-associated factors 11, 73 <BR />
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| [[3mhs]] – hUSP + SUS1 + SAGA-associated factors 11, 73 + Ub <BR />
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| [[3n3k]] – hUSP + Ub inhibitor <BR />
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| ''USP 15''
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| [[3lmn]] – hUSP DUSP domain <BR />
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| ''USP 16''
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| [[2i50]] – hUSP zinc finger domain - NMR <BR />
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| ''USP 21''
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| [[3i3t]] – hUSP + Ub <BR />
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| [[3mtn]] – hUSP + Ub inhibitor <BR />
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| ''USP 28''
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| [[2lva]] – hUSP N terminal - NMR <BR />
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| ''USP 33''
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| [[2uzg]] – hUSP zinc finger domain - NMR <BR />
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| ''USP 37''
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| [[3ihr]] – hUSP (mutant) <BR />
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| [[3a7s]] – hUSP catalytic domain (mutant) <BR />
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| ''USP Cyld''
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| [[2vhf]] – hUSP <BR />
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| ''USP L1''
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| [[3irt]] – hUSP (mutant) <BR />
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| [[2len]] – hUSP (mutant) - NMR<BR />
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| [[3ifw]], [[3kvf]], [[3kw5]] – hUSP (mutant) + Ub<BR />
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| [[4dm9]] – hUSP + peptide inhibitor<BR />
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| ''USP L5''
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| [[3ris]] – hUSP catalytic domain <BR />
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| [[3rii]] – hUSP catalytic domain (mutant) <BR />
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| [[3tb3]] – hUSP UCH domain (mutant) <BR />
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| ''USP ZranB1''
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| [[3zrh]] – hUSP <BR />
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| ''USP OTUB1''
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| [[3von]] – hUSP + E2 <BR />
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| [[4ddg]], [[4ddi]] – hUSP + Ub<BR />
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| [[4ddi]] – hUSP (mutant) + Ub<BR />
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| [[4dhz]] – hUSP + E2 + Ub<BR />
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| [[4dhj]] – nUSP + E2 + Ub - nematode<BR />
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| [[4dhi]] – nUSP + E2 <BR />
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| [[3znh]] – USP + Ub – Crimean-Congo hemorrhagic fever virus<BR />
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| '''RedJ TE'''
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| [[3qmv]], [[3qmw]] – TE –'' Streptomyces coelicolor''
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| [[2av9 ]]– TE – ''Pseudomonas aeruginosa''
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| | == References == |
| | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |