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2v5x
From Proteopedia
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| - | [[Image:2v5x. | + | [[Image:2v5x.jpg|left|200px]]<br /><applet load="2v5x" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2v5x" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="2v5x, resolution 2.25Å" /> | caption="2v5x, resolution 2.25Å" /> | ||
'''CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX'''<br /> | '''CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2V5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, K and V5X as [http://en.wikipedia.org/wiki/ligands ligands]. | + | 2V5X is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN, K and V5X as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Site: <scene name='pdbsite=AC1:V5x Binding Site For Chain B'>AC1</scene>. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V5X OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 20:29:07 2007'' |
Revision as of 18:19, 18 December 2007
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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 with ZN, K and V5X as ligands. Known structural/functional Site: . 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 Tue Dec 18 20:29:07 2007
Categories: Homo sapiens | Single protein | Carfi, A. | Defrancesco, R. | Gallinari, P. | Jones, P. | Marco, S.Di. | Mattu, M. | Steinkuhler, C. | Vannini, A. | Volpari, C. | K | V5X | ZN | 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
