|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of the UCH domain of UCH-L5 with 6 residues deleted== | | ==Crystal structure of the UCH domain of UCH-L5 with 6 residues deleted== |
| - | <StructureSection load='3tb3' size='340' side='right' caption='[[3tb3]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='3tb3' size='340' side='right'caption='[[3tb3]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3tb3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3sqa 3sqa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TB3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TB3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3tb3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3sqa 3sqa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TB3 FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AD-019, CGI-70, UCH-L5, UCH37, UCHL5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene></td></tr> |
| - | <tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3tb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tb3 OCA], [https://pdbe.org/3tb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tb3 RCSB], [https://www.ebi.ac.uk/pdbsum/3tb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tb3 ProSAT]</span></td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3tb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tb3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tb3 RCSB], [http://www.ebi.ac.uk/pdbsum/3tb3 PDBsum]</span></td></tr> | + | </table> |
| - | <table> | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/UCHL5_HUMAN UCHL5_HUMAN] Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.<ref>PMID:16906146</ref> <ref>PMID:18922472</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 14: |
Line 16: |
| | Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains.,Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY Biochem J. 2012 Jan 1;441(1):143-9. PMID:21851340<ref>PMID:21851340</ref> | | Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains.,Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY Biochem J. 2012 Jan 1;441(1):143-9. PMID:21851340<ref>PMID:21851340</ref> |
| | | | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3tb3" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Thioesterase|Thioesterase]] | + | *[[Thioesterase 3D structures|Thioesterase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| Line 24: |
Line 27: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Large Structures]] |
| - | [[Category: Hu, H Y.]] | + | [[Category: Hu HY]] |
| - | [[Category: Zha, M.]] | + | [[Category: Zha M]] |
| - | [[Category: Zhou, J.]] | + | [[Category: Zhou J]] |
| - | [[Category: Zhou, Z R.]] | + | [[Category: Zhou ZR]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Uch domain]]
| + | |
| Structural highlights
Function
UCHL5_HUMAN Protease that specifically cleaves 'Lys-48'-linked polyubiquitin chains. Deubiquitinating enzyme associated with the 19S regulatory subunit of the 26S proteasome. Putative regulatory component of the INO80 complex; however is inactive in the INO80 complex and is activated by a transient interaction of the INO80 complex with the proteasome via ADRM1.[1] [2]
Publication Abstract from PubMed
UCHs [Ub (ubiquitin) C-terminal hydrolases] are a family of deubiquitinating enzymes that are often thought to only remove small C-terminal peptide tails from Ub adducts. Among the four UCHs identified to date, neither UCH-L3 nor UCH-L1 can catalyse the hydrolysis of isopeptide Ub chains, but UCH-L5 can when it is present in the PA700 complex of the proteasome. In the present paper, we report that the UCH domain of UCH-L5, different from UCH-L1 and UCH-L3, by itself can process the K48-diUb (Lys48-linked di-ubiquitin) substrate by cleaving the isopeptide bond between two Ub units. The catalytic specificity of the four UCHs is dependent on the length of the active-site crossover loop. The UCH domain with a long crossover loop (usually >14 residues), such as that of UCH-L5 or BAP1 [BRCA1 (breast cancer early-onset 1)-associated protein 1], is able to cleave both small and large Ub derivatives, whereas the one with a short loop can only process small Ub derivatives. We also found that elongation of the crossover loop enables UCH-L1 to have isopeptidase activity for K48-diUb in a length-dependent manner. Thus the loop length of UCHs defines their substrate specificity for diUb chains, suggesting that the chain flexibility of the crossover loop plays an important role in determining its catalytic activity and substrate specificity for cleaving isopeptide Ub chains.
Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains.,Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY Biochem J. 2012 Jan 1;441(1):143-9. PMID:21851340[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yao T, Song L, Xu W, DeMartino GN, Florens L, Swanson SK, Washburn MP, Conaway RC, Conaway JW, Cohen RE. Proteasome recruitment and activation of the Uch37 deubiquitinating enzyme by Adrm1. Nat Cell Biol. 2006 Sep;8(9):994-1002. Epub 2006 Aug 13. PMID:16906146 doi:ncb1460
- ↑ Yao T, Song L, Jin J, Cai Y, Takahashi H, Swanson SK, Washburn MP, Florens L, Conaway RC, Cohen RE, Conaway JW. Distinct modes of regulation of the Uch37 deubiquitinating enzyme in the proteasome and in the Ino80 chromatin-remodeling complex. Mol Cell. 2008 Sep 26;31(6):909-17. doi: 10.1016/j.molcel.2008.08.027. PMID:18922472 doi:10.1016/j.molcel.2008.08.027
- ↑ Zhou ZR, Zhang YH, Liu S, Song AX, Hu HY. Length of the active-site crossover loop defines the substrate specificity of ubiquitin C-terminal hydrolases for ubiquitin chains. Biochem J. 2012 Jan 1;441(1):143-9. PMID:21851340 doi:http://dx.doi.org/10.1042/BJ20110699
|
