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4l3o

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{{STRUCTURE_4l3o| PDB=4l3o | SCENE= }}
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==Crystal Structure of SIRT2 in complex with the macrocyclic peptide S2iL5==
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===Crystal Structure of SIRT2 in complex with the macrocyclic peptide S2iL5===
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<StructureSection load='4l3o' size='340' side='right' caption='[[4l3o]], [[Resolution|resolution]] 2.52&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24389023}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4l3o]] is a 8 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=4L3O OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L3O FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=FAK:N~6~-(TRIFLUOROACETYL)-L-LYSINE'>FAK</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SIRT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<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=4l3o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l3o OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4l3o RCSB], [http://www.ebi.ac.uk/pdbsum/4l3o PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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SIRT2 deacetylates specific acetyllysine residues in diverse proteins and is implicated in a variety of cellular processes. SIRT2 inhibition thus has potentials to treat human diseases such as cancers and neurodegenerative disorders. We have recently developed a series of epsilon-trifluoroacetyllysine-containing macrocyclic peptides, which inhibit the SIRT2 activity more potently than most other known inhibitors. Here, we report the crystal structure of human SIRT2 in complex with a macrocyclic peptide inhibitor, S2iL5, at 2.5 A resolution. The structure revealed that S2iL5 binds to the active site of SIRT2 through extensive interactions. A structural comparison of the SIRT2-S2iL5 complex with SIRT2 in the free form, and in complex with ADP-ribose, revealed that S2iL5 induces an open-to-closed domain movement and an unexpected helix-to-coil transition in a SIRT2-specific region. Our findings unveil the potential of macrocyclic peptides to bind target proteins by inducing dynamic structural changes.
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==Function==
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Structural Basis for Potent Inhibition of SIRT2 Deacetylase by a Macrocyclic Peptide Inducing Dynamic Structural Change.,Yamagata K, Goto Y, Nishimasu H, Morimoto J, Ishitani R, Dohmae N, Takeda N, Nagai R, Komuro I, Suga H, Nureki O Structure. 2014 Feb 4;22(2):345-52. doi: 10.1016/j.str.2013.12.001. Epub 2014 Jan, 2. PMID:24389023<ref>PMID:24389023</ref>
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[[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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4l3o]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L3O OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:024389023</ref><references group="xtra"/><references/>
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__TOC__
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[[Category: Ishitani, R.]]
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</StructureSection>
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[[Category: Nishimasu, H.]]
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[[Category: Human]]
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[[Category: Nureki, O.]]
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[[Category: Ishitani, R]]
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[[Category: Yamagata, K.]]
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[[Category: Nishimasu, H]]
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[[Category: Nureki, O]]
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[[Category: Yamagata, K]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Hydrolase-hydrolase inhibitor complex]]
[[Category: Macrocyclic peptide]]
[[Category: Macrocyclic peptide]]
[[Category: Structural change]]
[[Category: Structural change]]

Revision as of 16:41, 21 December 2014

Crystal Structure of SIRT2 in complex with the macrocyclic peptide S2iL5

4l3o, resolution 2.52Å

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