2v5x: Difference between revisions
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<StructureSection load='2v5x' size='340' side='right'caption='[[2v5x]], [[Resolution|resolution]] 2.25Å' scene=''> | <StructureSection load='2v5x' size='340' side='right'caption='[[2v5x]], [[Resolution|resolution]] 2.25Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2v5x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2v5x]] 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=2V5X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V5X FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=V5X:(2R)-N~8~-HYDROXY-2-{[(5-METHOXY-2-METHYL-1H-INDOL-3-YL)ACETYL]AMINO}-N~1~-[2-(2-PHENYL-1H-INDOL-3-YL)ETHYL]OCTANEDIAMIDE'>V5X</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=V5X:(2R)-N~8~-HYDROXY-2-{[(5-METHOXY-2-METHYL-1H-INDOL-3-YL)ACETYL]AMINO}-N~1~-[2-(2-PHENYL-1H-INDOL-3-YL)ETHYL]OCTANEDIAMIDE'>V5X</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'>[https://proteopedia.org/fgij/fg.htm?mol=2v5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5x OCA], [https://pdbe.org/2v5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v5x RCSB], [https://www.ebi.ac.uk/pdbsum/2v5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5x 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=2v5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5x OCA], [https://pdbe.org/2v5x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v5x RCSB], [https://www.ebi.ac.uk/pdbsum/2v5x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v5x ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/HDAC8_HUMAN HDAC8_HUMAN] Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. May play a role in smooth muscle cell contractility.<ref>PMID:10748112</ref> <ref>PMID:10926844</ref> <ref>PMID:10922473</ref> <ref>PMID:14701748</ref> | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Carfi | [[Category: Carfi A]] | ||
[[Category: Defrancesco | [[Category: Defrancesco R]] | ||
[[Category: | [[Category: Di Marco S]] | ||
[[Category: | [[Category: Gallinari P]] | ||
[[Category: | [[Category: Jones P]] | ||
[[Category: Mattu | [[Category: Mattu M]] | ||
[[Category: Steinkuhler | [[Category: Steinkuhler C]] | ||
[[Category: Vannini | [[Category: Vannini A]] | ||
[[Category: Volpari | [[Category: Volpari C]] | ||
Latest revision as of 18:07, 13 December 2023
Crystal structure of HDAC8-inhibitor complexCrystal structure of HDAC8-inhibitor complex
Structural highlights
FunctionHDAC8_HUMAN Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. May play a role in smooth muscle cell contractility.[1] [2] [3] [4] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHistone deacetylases (HDACs)-an enzyme family that deacetylates histones and non-histone proteins-are implicated in human diseases such as cancer, and the first-generation of HDAC inhibitors are now in clinical trials. Here, we report the 2.0 A resolution crystal structure of a catalytically inactive HDAC8 active-site mutant, Tyr306Phe, bound to an acetylated peptidic substrate. The structure clarifies the role of active-site residues in the deacetylation reaction and substrate recognition. Notably, the structure shows the unexpected role of a conserved residue at the active-site rim, Asp 101, in positioning the substrate by directly interacting with the peptidic backbone and imposing a constrained cis-conformation. A similar interaction is observed in a new hydroxamate inhibitor-HDAC8 structure that we also solved. The crucial role of Asp 101 in substrate and inhibitor recognition was confirmed by activity and binding assays of wild-type HDAC8 and Asp101Ala, Tyr306Phe and Asp101Ala/Tyr306Phe mutants. Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex.,Vannini A, Volpari C, Gallinari P, Jones P, Mattu M, Carfi A, De Francesco R, Steinkuhler C, Di Marco S EMBO Rep. 2007 Sep;8(9):879-84. Epub 2007 Aug 10. PMID:17721440[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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