5dy5: Difference between revisions

Line 1:

'''~~Unreleased~~ structure'''

==Crystal structure of human Sirt2 in complex with a SirReal probe fragment==

== Structural highlights ==

<table><tr><td colspan='2'>[[5dy5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DY5 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GR:N-(5-{3-[(1-BENZYL-1H-1,2,3-TRIAZOL-4-YL)METHOXY]BENZYL}-1,3-THIAZOL-2-YL)-2-[(4,6-DIMETHYLPYRIMIDIN-2-YL)SULFANYL]ACETAMIDE'>5GR</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5dy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dy5 OCA], [http://pdbe.org/5dy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dy5 RCSB], [http://www.ebi.ac.uk/pdbsum/5dy5 PDBsum]</span></td></tr>

</table>

== 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>

== Publication Abstract from PubMed ==

Sirtuins are NAD+ -dependent protein deacylases that cleave off acetyl groups, as well as other acyl groups, from the epsilon-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, thus making Sirt2 a promising target for pharmaceutical intervention. Here, based on a crystal structure of Sirt2 in complex with an optimized sirtuin rearranging ligand (SirReal) that shows improved potency, water solubility, and cellular efficacy, we present the development of the first Sirt2-selective affinity probe. A slow dissociation of the probe/enzyme complex offers new applications for SirReals, such as biophysical characterization, fragment-based screening, and affinity pull-down assays. This possibility makes the SirReal probe an important tool for studying sirtuin biology.

~~The entry 5dy5 is ON HOLD until Paper Publication~~

Structure-Based Development of an Affinity Probe for Sirtuin 2.,Schiedel M, Rumpf T, Karaman B, Lehotzky A, Gerhardt S, Ovadi J, Sippl W, Einsle O, Jung M Angew Chem Int Ed Engl. 2016 Jan 8. doi: 10.1002/anie.201509843. PMID:26748890<ref>PMID:26748890</ref>

~~Authors: Rumpf~~, T.~~, Gerhardt,~~ S.~~, Einsle, O., Jung, M~~.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~Description~~: ~~Crystal structure of human Sirt2 in complex with a SirReal probe fragment~~

~~[[Category: Unreleased Structures]]~~

== References ==

[[Category: ~~Rumpf~~, T]]

__TOC__

</StructureSection>

[[Category: Einsle, O]]

[[Category: Gerhardt, S]]

[[Category: Jung, M]]

[[Category: ~~Einsle~~, O]]

[[Category: Rumpf, T]]

[[Category: Hydrolase]]

[[Category: Hydrolase inhibitor complex]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==Crystal structure of human Sirt2 in complex with a SirReal probe fragment==
+<StructureSection load='5dy5' size='340' side='right' caption='[[5dy5]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5dy5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DY5 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5GR:N-(5-{3-[(1-BENZYL-1H-1,2,3-TRIAZOL-4-YL)METHOXY]BENZYL}-1,3-THIAZOL-2-YL)-2-[(4,6-DIMETHYLPYRIMIDIN-2-YL)SULFANYL]ACETAMIDE'>5GR</scene>, <scene name='pdbligand=BU3:(R,R)-2,3-BUTANEDIOL'>BU3</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=5dy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dy5 OCA], [http://pdbe.org/5dy5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5dy5 RCSB], [http://www.ebi.ac.uk/pdbsum/5dy5 PDBsum]</span></td></tr>
+</table>
+== 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Sirtuins are NAD+ -dependent protein deacylases that cleave off acetyl groups, as well as other acyl groups, from the epsilon-amino group of lysines in histones and other substrate proteins. Dysregulation of human Sirt2 activity has been associated with the pathogenesis of cancer, inflammation, and neurodegeneration, thus making Sirt2 a promising target for pharmaceutical intervention. Here, based on a crystal structure of Sirt2 in complex with an optimized sirtuin rearranging ligand (SirReal) that shows improved potency, water solubility, and cellular efficacy, we present the development of the first Sirt2-selective affinity probe. A slow dissociation of the probe/enzyme complex offers new applications for SirReals, such as biophysical characterization, fragment-based screening, and affinity pull-down assays. This possibility makes the SirReal probe an important tool for studying sirtuin biology.
-The entry 5dy5 is ON HOLD  until Paper Publication
+Structure-Based Development of an Affinity Probe for Sirtuin 2.,Schiedel M, Rumpf T, Karaman B, Lehotzky A, Gerhardt S, Ovadi J, Sippl W, Einsle O, Jung M Angew Chem Int Ed Engl. 2016 Jan 8. doi: 10.1002/anie.201509843. PMID:26748890<ref>PMID:26748890</ref>
-Authors: Rumpf, T., Gerhardt, S., Einsle, O., Jung, M.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: Crystal structure of human Sirt2 in complex with a SirReal probe fragment
+<div class="pdbe-citations 5dy5" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Rumpf, T]]
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Einsle, O]]
 [[Category: Gerhardt, S]]
 [[Category: Jung, M]]
-[[Category: Einsle, O]]
+[[Category: Rumpf, T]]
+[[Category: Hydrolase]]
+[[Category: Hydrolase inhibitor complex]]