This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2ovm

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2ovm.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2ovm.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2ovm| PDB=2ovm | SCENE= }}
{{STRUCTURE_2ovm| PDB=2ovm | SCENE= }}
-
'''Progesterone Receptor with Bound Asoprisnil and a Peptide from the Co-Repressor NCoR'''
+
===Progesterone Receptor with Bound Asoprisnil and a Peptide from the Co-Repressor NCoR===
-
==Overview==
+
<!--
-
Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone receptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17356170}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17356170 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17356170}}
==About this Structure==
==About this Structure==
Line 34: Line 38:
[[Category: Progesterone receptor]]
[[Category: Progesterone receptor]]
[[Category: Steroid receptor]]
[[Category: Steroid receptor]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 11:45:14 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 16:12:45 2008''

Revision as of 13:12, 28 July 2008

Image:2ovm.png

Template:STRUCTURE 2ovm

Progesterone Receptor with Bound Asoprisnil and a Peptide from the Co-Repressor NCoR

Template:ABSTRACT PUBMED 17356170

About this Structure

2OVM is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator., Madauss KP, Grygielko ET, Deng SJ, Sulpizio AC, Stanley TB, Wu C, Short SA, Thompson SK, Stewart EL, Laping NJ, Williams SP, Bray JD, Mol Endocrinol. 2007 May;21(5):1066-81. Epub 2007 Mar 13. PMID:17356170

Page seeded by OCA on Mon Jul 28 16:12:45 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ovm"
Personal tools