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| | <StructureSection load='5d7o' size='340' side='right'caption='[[5d7o]], [[Resolution|resolution]] 1.63Å' scene=''> | | <StructureSection load='5d7o' size='340' side='right'caption='[[5d7o]], [[Resolution|resolution]] 1.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5d7o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D7O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D7O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5d7o]] is a 2 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=5D7O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D7O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR6:[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+[HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL]+HYDROGEN+PHOSPHATE'>AR6</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIRT2, SIR2L, SIR2L2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5d7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d7o OCA], [https://pdbe.org/5d7o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d7o RCSB], [https://www.ebi.ac.uk/pdbsum/5d7o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d7o ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5d7o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d7o OCA], [http://pdbe.org/5d7o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d7o RCSB], [http://www.ebi.ac.uk/pdbsum/5d7o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d7o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/SIR2_HUMAN SIR2_HUMAN]] NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.<ref>PMID:12620231</ref> <ref>PMID:12697818</ref> <ref>PMID:21081649</ref> <ref>PMID:21726808</ref> | + | [https://www.uniprot.org/uniprot/SIR2_HUMAN SIR2_HUMAN] NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.<ref>PMID:12620231</ref> <ref>PMID:12697818</ref> <ref>PMID:21081649</ref> <ref>PMID:21726808</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: Einsle, O]] | + | [[Category: Einsle O]] |
| - | [[Category: Gerhardt, S]] | + | [[Category: Gerhardt S]] |
| - | [[Category: Jung, M]] | + | [[Category: Jung M]] |
| - | [[Category: Rumpf, T]] | + | [[Category: Rumpf T]] |
| - | [[Category: Deacylase]]
| + | |
| - | [[Category: Human sirt2]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| Structural highlights
Function
SIR2_HUMAN NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.[1] [2] [3] [4]
Publication Abstract from PubMed
Sirtuins constitute a family of NAD(+)-dependent enzymes that catalyse the cleavage of various acyl groups from the -amino group of lysines. They regulate a series of cellular processes and their misregulation has been implicated in various diseases, making sirtuins attractive drug targets. To date, only a few sirtuin modulators have been reported that are suitable for cellular research and their development has been hampered by a lack of structural information. In this work, microseed matrix seeding (MMS) was used to obtain crystals of human Sirt3 in its apo form and of human Sirt2 in complex with ADP ribose (ADPR). Crystal formation using MMS was predictable, less error-prone and yielded a higher number of crystals per drop than using conventional crystallization screening methods. The crystals were used to solve the crystal structures of apo Sirt3 and of Sirt2 in complex with ADPR at an improved resolution, as well as the crystal structures of Sirt2 in complex with ADPR and the indoles EX527 and CHIC35. These Sirt2-ADPR-indole complexes unexpectedly contain two indole molecules and provide novel insights into selective Sirt2 inhibition. The MMS approach for Sirt2 and Sirt3 may be used as the basis for structure-based optimization of Sirt2/3 inhibitors in the future.
Seeding for sirtuins: microseed matrix seeding to obtain crystals of human Sirt3 and Sirt2 suitable for soaking.,Rumpf T, Gerhardt S, Einsle O, Jung M Acta Crystallogr F Struct Biol Commun. 2015 Dec 1;71(Pt 12):1498-510. doi:, 10.1107/S2053230X15019986. Epub 2015 Nov 18. PMID:26625292[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. PMID:12620231
- ↑ Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May;23(9):3173-85. PMID:12697818
- ↑ Rothgiesser KM, Erener S, Waibel S, Luscher B, Hottiger MO. SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8. doi: 10.1242/jcs.073783. Epub 2010 Nov, 16. PMID:21081649 doi:10.1242/jcs.073783
- ↑ Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011 Jul 8;43(1):33-44. doi: 10.1016/j.molcel.2011.04.028. PMID:21726808 doi:10.1016/j.molcel.2011.04.028
- ↑ Rumpf T, Gerhardt S, Einsle O, Jung M. Seeding for sirtuins: microseed matrix seeding to obtain crystals of human Sirt3 and Sirt2 suitable for soaking. Acta Crystallogr F Struct Biol Commun. 2015 Dec 1;71(Pt 12):1498-510. doi:, 10.1107/S2053230X15019986. Epub 2015 Nov 18. PMID:26625292 doi:http://dx.doi.org/10.1107/S2053230X15019986
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