2v5x: Difference between revisions

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[[Image:2v5x.~~jpg~~|left|200px]]

[[Image:2v5x.png|left|200px]]

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~~'''~~CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX~~'''~~

===CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX===

~~==Overview==~~

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~~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.~~

The line below this paragraph, {{ABSTRACT_PUBMED_17721440}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 17721440 is the PubMed ID number.

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==About this Structure==

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[[Category: Transcription]]

[[Category: Transcription regulation]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun ~~May 4 18~~:14:08 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:33:27 2008''

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-[[Image:2v5x.jpg|left|200px]]
+{{Seed}}
+[[Image:2v5x.png|left|200px]]
 <!--
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 {{STRUCTURE_2v5x|  PDB=2v5x  |  SCENE=  }}
-'''CRYSTAL STRUCTURE OF HDAC8-INHIBITOR COMPLEX'''
+===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.
+The line below this paragraph, {{ABSTRACT_PUBMED_17721440}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 17721440 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_17721440}}
 ==About this Structure==
@@ Line 48: / Line 52: @@
 [[Category: Transcription]]
 [[Category: Transcription regulation]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 18:14:08 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 17:33:27 2008''