2v5x: Difference between revisions
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|PDB= 2v5x |SIZE=350|CAPTION= <scene name='initialview01'>2v5x</scene>, resolution 2.25Å | |PDB= 2v5x |SIZE=350|CAPTION= <scene name='initialview01'>2v5x</scene>, resolution 2.25Å | ||
|SITE= <scene name='pdbsite=AC1:V5x+Binding+Site+For+Chain+B'>AC1</scene> | |SITE= <scene name='pdbsite=AC1:V5x+Binding+Site+For+Chain+B'>AC1</scene> | ||
|LIGAND= | |LIGAND= <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> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1t64|1T64]], [[1t67|1T67]], [[1t69|1T69]], [[1vkg|1VKG]], [[1w22|1W22]], [[2v5w|2V5W]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2v5x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v5x OCA], [http://www.ebi.ac.uk/pdbsum/2v5x PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2v5x RCSB]</span> | |||
}} | }} | ||
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[[Category: Vannini, A.]] | [[Category: Vannini, A.]] | ||
[[Category: Volpari, C.]] | [[Category: Volpari, C.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: chromatin]] | [[Category: chromatin]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
''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 05:08:38 2008'' | ||
Revision as of 02:08, 31 March 2008
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| 2v5x, resolution 2.25Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Sites: | AC1 | ||||||||||||
| Ligands: | K, V5X, ZN | ||||||||||||
| Related: | 1T64, 1T67, 1T69, 1VKG, 1W22, 2V5W
| ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX
Overview
Histone 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.
About this Structure
2V5X is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Mon Mar 31 05:08:38 2008
Proteopedia Page Contributors and Editors (what is this?)
- Pages with broken file links
- Homo sapiens
- Single protein
- Carfi, A.
- Defrancesco, R.
- Gallinari, P.
- Jones, P.
- Marco, S Di.
- Mattu, M.
- Steinkuhler, C.
- Vannini, A.
- Volpari, C.
- Alternative splicing
- Chromatin
- Chromatin regulator
- Deacetylation
- Drug design
- Hdac
- Hdac8
- Histone deacetylase
- Hydrolase
- Hydroxamate inhibitor
- Nuclear protein
- Nucleus
- P53
- Peptidic substrate
- Repressor
- Transcription
- Transcription regulation
