Linked Life Data

16681389

Source:http://linkedlifedata.com/resource/pubmed/id/16681389

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2006-5-9
pubmed:abstractText
Histone deacetylases play a key role in regulating transcription and other cellular processes by catalyzing the hydrolysis of epsilon-acetyl-lysine residues. For this reason, inhibitors of histone deacetylases are potential targets for the treatment of cancer. A subset of these enzymes has previously been shown to require divalent metal ions for catalysis. Here we demonstrate that histone deacetylase 8 (HDAC8) is catalytically active with a number of divalent metal ions in a 1:1 stoichiometry with the following order of specific activity: Co(II) > Fe(II) > Zn(II) > Ni(II). The identity of the catalytic metal ion influences both the affinity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the Michaelis constant, with Fe(II)- and Co(II)-HDAC8 having K(M) values that are over 5-fold lower than that of Zn(II)-HDAC8. These data suggest that Fe(II), rather than Zn(II), may be the in vivo catalytic metal. In further support of this hypothesis, recombinant HDAC8 purified from E. coli contains 8-fold more iron than zinc before dialysis, and the HDAC8 activity in cell lysates is oxygen-sensitive. Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6170-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Catalytic activity and inhibition of human histone deacetylase 8 is dependent on the identity of the active site metal ion.
pubmed:affiliation
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural