Linked Life Data

19355988

Source:http://linkedlifedata.com/resource/pubmed/id/19355988

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-4-9
pubmed:abstractText
The deacetylation of modified lysine residues of histones and other proteins is catalyzed by histone deacetlyases (HDACs). HDACs play an important role in the regulation of many biological processes such as cell-cycle, cell differentiation and survival. Since the inhibition of HDACs leads to growth arrest, differentiation or apoptosis of tumor cell lines, HDACs are promising targets for cancer therapy. Knowledge of the three-dimensional structures of HDACs with bound substrate or inhibitor molecules is a prerequisite for rational structure-based drug design. Here recent developments in the crystal structure analysis of human HDAC4, HDAC7, and HDAC8, which all belong to the family of zinc ion-dependent HDACs, are described. Crystallographic and biochemical studies of the catalytic domains of HDAC4 and HDAC7 revealed the molecular basis for their low enzymatic activity. Furthermore, the role of a second, structural zinc ion has been elucidated. The structures of HDAC8 with bound substrate-like peptide molecule demonstrate the functional role of a conserved aspartate residue located at the rim of the active site in substrate recognition. Structures of these three HDACs with various bound inhibitor molecules will provide the structural basis for further development of HDAC inhibitors with improved isoform-specific selectivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1873-4294
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
235-40
pubmed:dateRevised
2009-12-11
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Novel structural insights into class I and II histone deacetylases.
pubmed:affiliation
Department of Molecular Structural Biology, Institute for Microbiology and Genetics, GZMB, Georg-August-University Göttingen, 37077 Göttingen, Germany. rficner@uni-goettingen.de
pubmed:publicationType
Journal Article, Review