Linked Life Data

21262235

Source:http://linkedlifedata.com/resource/pubmed/id/21262235

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-2-28
pubmed:databankReference
pubmed:abstractText
The nuclear receptor retinoid X receptor (RXR) functions potently in the regulation of homeostasis and cell development, while rexinoids as RXR agonists have proved their therapeutic potential in the treatment of metabolic diseases and cancer. Here, the natural product bigelovin was identified as a selective RXR? agonist. Interestingly, this compound could not transactivate RXR?:RXR? homodimer but could enhance the transactivation of RXR?:peroxisome proliferator-activated receptor ? heterodimer and repress that of RXR?:liver X receptor (LXR) ? heterodimer, while it had no effects on RXR?:farnesoid X receptor heterodimer. Considering that the effective role of LXR response element involved transactivation of sterol regulatory element-binding protein-1c mediated by RXR?:LXR? in triglyceride elevation, such LXR response element repressing by bigelovin has obviously addressed its potency for further research. Moreover, our determined crystal structure of the bigelovin-activated RXR? ligand-binding domain with the coactivator human steroid receptor coactivator-1 peptide revealed that bigelovin adopted a distinct binding mode. Compared with the known RXR ligands, bigelovin lacks the acidic moiety in structure, which indicated that the acidic moiety rendered little effects on RXR activation. Our results have thereby provided new insights into the structure-based selective rexinoids design with bigelovin as a potential lead compound.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
407
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-20
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structure basis of bigelovin as a selective RXR agonist with a distinct binding mode.
pubmed:affiliation
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't