Linked Life Data

18729348

Source:http://linkedlifedata.com/resource/pubmed/id/18729348

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2008-9-19
pubmed:abstractText
Previously, we designed and synthesized a potent NF-kappaB inhibitor, DHMEQ. Although DHMEQ showed potent anti-inflammatory and anticancer activities in animals, its molecular target has not been elucidated. In the present study, its target protein was found to be p65 and other Rel homology proteins. We found that (-)-DHMEQ bound to p65 covalently with a 1:1 stoichiometry by conducting SPR and MALDI-TOF MS analyses. MS analysis of the chymotrypsin-digested peptide suggested the binding of (-)-DHMEQ to a Cys residue. Formation of Cys/(-)-DHMEQ adduct in the protein was supported by chemical synthesis of the adduct. Substitution of specific Cys in p65 and other Rel homology proteins resulted in the loss of (-)-DHMEQ binding. (-)-DHMEQ is the first NF-kappaB inhibitor that was proven to bind to the specific Cys by chemical methodology. These findings may explain the highly selective inhibition of NF-kappaB and the low toxic effect of (-)-DHMEQ in cells and animals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5780-8
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Inactivation of NF-kappaB components by covalent binding of (-)-dehydroxymethylepoxyquinomicin to specific cysteine residues.
pubmed:affiliation
Center for Chemical Biology, School of Fundamental Science and Technology, Keio University, Yokohama 223-0061, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't