18412327

Source:http://linkedlifedata.com/resource/pubmed/id/18412327

Download in:

Switch to

Custom View

Named Graph Language Inference

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0439659, umls-concept:C0456387, umls-concept:C0678594, umls-concept:C1512474, umls-concept:C2266853
pubmed:issue	10
pubmed:dateCreated	2008-5-15
pubmed:abstractText	The development of class- and isoform-selective histone deacetylase (HDAC) inhibitors is highly desirable for the study of the complex interactions of these proteins central to transcription regulation as well as for the development of selective HDAC inhibitors as drugs in epigenetics. To provide a structural basis for the rational design of such inhibitors, a combined computational and experimental study of inhibition of three different histone deacetylase isoforms, HDAC1, -6, and -8, with three different hydroxamate inhibitors is reported. While SAHA was found to be unselective for the inhibition of class I and class II HDACs, the other inhibitors were found to be selective toward class II HDACs. Molecular dynamics simulations indicate that this selectivity is caused by both the overall shape of the protein surface leading to the active site and specific interactions of an aspartate residue in a polar loop and two phenylalanines and a methionine in a nonpolar loop. Monitoring the specific interactions as a function of the simulation time identifies a key sulfur-pi interaction. The implications of the structural motifs for the design of class II-selective HDAC inhibitors are discussed.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/9716531
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Anilides, http://linkedlifedata.com/resource/pubmed/chemical/HDAC1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HDAC6 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/HDAC8 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase 1, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases, http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes, http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/tubacin, http://linkedlifedata.com/resource/pubmed/chemical/vorinostat
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	0022-2623
pubmed:author	pubmed-author:BradnerJames EJE, pubmed-author:EstiuGuillerminaG, pubmed-author:GreenbergEdwardE, pubmed-author:HarrisonChristopher BCB, pubmed-author:KwiatkowskiNicholas PNP, pubmed-author:MazitschekRalphR, pubmed-author:WiestOlafO
pubmed:issnType	Print
pubmed:day	22
pubmed:volume	51
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	2898-906
pubmed:dateRevised	2009-11-19
pubmed:meshHeading	pubmed-meshheading:18412327-Anilides, pubmed-meshheading:18412327-Crystallography, X-Ray, pubmed-meshheading:18412327-Histone Deacetylase 1, pubmed-meshheading:18412327-Histone Deacetylase Inhibitors, pubmed-meshheading:18412327-Histone Deacetylases, pubmed-meshheading:18412327-Hydroxamic Acids, pubmed-meshheading:18412327-Isoenzymes, pubmed-meshheading:18412327-Models, Molecular, pubmed-meshheading:18412327-Protein Conformation, pubmed-meshheading:18412327-Repressor Proteins, pubmed-meshheading:18412327-Structure-Activity Relationship
pubmed:year	2008
pubmed:articleTitle	Structural origin of selectivity in class II-selective histone deacetylase inhibitors.
pubmed:affiliation	Walther Cancer Research Center, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556-5670, USA.
pubmed:publicationType	Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural