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| | <StructureSection load='6z49' size='340' side='right'caption='[[6z49]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='6z49' size='340' side='right'caption='[[6z49]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6z49]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z49 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6z49]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6Z49 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Z49 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MINDY2, FAM63B, KIAA1164 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [https://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=6z49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z49 OCA], [https://pdbe.org/6z49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z49 RCSB], [https://www.ebi.ac.uk/pdbsum/6z49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z49 ProSAT]</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=6z49 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6z49 OCA], [https://pdbe.org/6z49 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6z49 RCSB], [https://www.ebi.ac.uk/pdbsum/6z49 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6z49 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/MINY2_HUMAN MINY2_HUMAN]] Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).<ref>PMID:27292798</ref> <ref>PMID:28082312</ref>
| + | [https://www.uniprot.org/uniprot/MINY2_HUMAN MINY2_HUMAN] Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).<ref>PMID:27292798</ref> <ref>PMID:28082312</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ubiquitinyl hydrolase 1]] | + | [[Category: Abdul Rehman SA]] |
| - | [[Category: Kulathu, Y]] | + | [[Category: Kulathu Y]] |
| - | [[Category: Rehman, S A.Abdul]]
| + | |
| - | [[Category: Cysteine protease]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Isopeptidase and ubiquitin binding]]
| + | |
| Structural highlights
Function
MINY2_HUMAN Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).[1] [2]
Publication Abstract from PubMed
Of the eight distinct polyubiquitin (polyUb) linkages that can be assembled, the roles of K48-linked polyUb (K48-polyUb) are the most established, with K48-polyUb modified proteins being targeted for degradation. MINDY1 and MINDY2 are members of the MINDY family of deubiquitinases (DUBs) that have exquisite specificity for cleaving K48-polyUb, yet we have a poor understanding of their catalytic mechanism. Here, we analyze the crystal structures of MINDY1 and MINDY2 alone and in complex with monoUb, di-, and penta-K48-polyUb, identifying 5 distinct Ub binding sites in the catalytic domain that explain how these DUBs sense both Ub chain length and linkage type to cleave K48-polyUb chains. The activity of MINDY1/2 is inhibited by the Cys-loop, and we find that substrate interaction relieves autoinhibition to activate these DUBs. We also find that MINDY1/2 use a non-canonical catalytic triad composed of Cys-His-Thr. Our findings highlight multiple layers of regulation modulating DUB activity in MINDY1 and MINDY2.
Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2.,Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI, Kulathu Y Mol Cell. 2021 Sep 10. pii: S1097-2765(21)00691-2. doi:, 10.1016/j.molcel.2021.08.024. PMID:34529927[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Abdul Rehman SA, Kristariyanto YA, Choi SY, Nkosi PJ, Weidlich S, Labib K, Hofmann K, Kulathu Y. MINDY-1 Is a Member of an Evolutionarily Conserved and Structurally Distinct New Family of Deubiquitinating Enzymes. Mol Cell. 2016 Jul 7;63(1):146-55. doi: 10.1016/j.molcel.2016.05.009. Epub 2016, Jun 9. PMID:27292798 doi:http://dx.doi.org/10.1016/j.molcel.2016.05.009
- ↑ Kristariyanto YA, Abdul Rehman SA, Weidlich S, Knebel A, Kulathu Y. A single MIU motif of MINDY-1 recognizes K48-linked polyubiquitin chains. EMBO Rep. 2017 Jan 12. pii: e201643205. doi: 10.15252/embr.201643205. PMID:28082312 doi:http://dx.doi.org/10.15252/embr.201643205
- ↑ Abdul Rehman SA, Armstrong LA, Lange SM, Kristariyanto YA, Grawert TW, Knebel A, Svergun DI, Kulathu Y. Mechanism of activation and regulation of deubiquitinase activity in MINDY1 and MINDY2. Mol Cell. 2021 Sep 10. pii: S1097-2765(21)00691-2. doi:, 10.1016/j.molcel.2021.08.024. PMID:34529927 doi:http://dx.doi.org/10.1016/j.molcel.2021.08.024
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