1w22: Difference between revisions
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|PDB= 1w22 |SIZE=350|CAPTION= <scene name='initialview01'>1w22</scene>, resolution 2.5Å | |PDB= 1w22 |SIZE=350|CAPTION= <scene name='initialview01'>1w22</scene>, resolution 2.5Å | ||
|SITE= <scene name='pdbsite=AC1:Nhb+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:Nhb+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= | |LIGAND= <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NHB:N-HYDROXY-4-(METHYL{[5-(2-PYRIDINYL)-2-THIENYL]SULFONYL}AMINO)BENZAMIDE'>NHB</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY= | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w22 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w22 OCA], [http://www.ebi.ac.uk/pdbsum/1w22 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w22 RCSB]</span> | |||
}} | }} | ||
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[[Category: Vannini, A.]] | [[Category: Vannini, A.]] | ||
[[Category: Volpari, C.]] | [[Category: Volpari, C.]] | ||
[[Category: chromatin]] | [[Category: chromatin]] | ||
[[Category: deacetylation]] | [[Category: deacetylation]] | ||
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[[Category: hydroxamic acid]] | [[Category: hydroxamic acid]] | ||
[[Category: nuclear protein]] | [[Category: nuclear protein]] | ||
[[Category: repressor]] | [[Category: repressor,]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:30:01 2008'' | ||
Revision as of 00:30, 31 March 2008
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| , resolution 2.5Å | |||||||
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| Ligands: | , , | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF INHIBITED HUMAN HDAC8
OverviewOverview
Histone deacetylases (HDACs) are a family of enzymes involved in the regulation of gene expression, DNA repair, and stress response. These processes often are altered in tumors, and HDAC inhibitors have had pronounced antitumor activity with promising results in clinical trials. Here, we report the crystal structure of human HDAC8 in complex with a hydroxamic acid inhibitor. Such a structure of a eukaryotic zinc-dependent HDAC has not be described previously. Similar to bacterial HDAC-like protein, HDAC8 folds in a single alpha/beta domain. The inhibitor and the zinc-binding sites are similar in both proteins. However, significant differences are observed in the length and structure of the loops surrounding the active site, including the presence of two potassium ions in HDAC8 structure, one of which interacts with key catalytic residues. CD data suggest a direct role of potassium in the fold stabilization of HDAC8. Knockdown of HDAC8 by RNA interference inhibits growth of human lung, colon, and cervical cancer cell lines, highlighting the importance of this HDAC subtype for tumor cell proliferation. Our findings open the way for the design and development of selective inhibitors of HDAC8 as possible antitumor agents.
About this StructureAbout this Structure
1W22 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor., Vannini A, Volpari C, Filocamo G, Casavola EC, Brunetti M, Renzoni D, Chakravarty P, Paolini C, De Francesco R, Gallinari P, Steinkuhler C, Di Marco S, Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15064-9. Epub 2004 Oct 11. PMID:15477595
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