Linked Life Data

7629162

Source:http://linkedlifedata.com/resource/pubmed/id/7629162

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
1995-9-7
pubmed:abstractText
Retinoic acid receptor-beta (RAR-beta) specifically binds retinoic acid (RA) and functions as a RA-inducible transcriptional regulatory factor. Simultaneous mutation of Arg269 and Lys220 of RAR-beta to Ala results in a dramatic reduction in both transactivation and affinity for RA along with creating a RA concentration-dependent dominant negative mutant. In this report, we found that mutation of these two amino acid residues singly and simultaneously to Gln results in mutant RAR-beta s, each displaying a more dramatic reduction in transactivation and affinity for RA than their corresponding Ala mutant, with the R269Q more profoundly affected than K220Q. Furthermore, we examined both the Ala and Gln mutants for their ability to transactivate and bind two other retinoids with different functional end groups (all-trans-retinol and all-trans-retinal). Mutation of Lys220 to either an Ala or a Gln favors transactivation and binding of retinal, while mutation of either Lys220 or Arg269 to Gln favors retinol transactivation and binding. Taken together, these results suggest that Arg269 and Lys220 lie within the ligand binding pocket of RAR-beta and Lys220 lie within the ligand binding pocket of RAR-beta and that these two amino acid residues play an important role in determining retinoid specificity most likely by directly interacting with the carboxylate group of RA.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18380-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Alteration in the retinoid specificity of retinoic acid receptor-beta by site-directed mutagenesis of Arg269 and Lys220.
pubmed:affiliation
Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.