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2q59

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[[Image:2q59.jpg|left|200px]]
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{{STRUCTURE_2q59| PDB=2q59 | SCENE= }}
{{STRUCTURE_2q59| PDB=2q59 | SCENE= }}
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'''Crystal Structure of PPARgamma LBD bound to full agonist MRL20'''
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===Crystal Structure of PPARgamma LBD bound to full agonist MRL20===
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==Overview==
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Binding to helix 12 of the ligand-binding domain of PPARgamma is required for full agonist activity. Previously, the degree of stabilization of the activation function 2 (AF-2) surface was thought to correlate with the degree of agonism and transactivation. To examine this mechanism, we probed structural dynamics of PPARgamma with agonists that induced graded transcriptional responses. Here we present crystal structures and amide H/D exchange (HDX) kinetics for six of these complexes. Amide HDX revealed each ligand induced unique changes to the dynamics of the ligand-binding domain (LBD). Full agonists stabilized helix 12, whereas intermediate and partial agonists did not at all, and rather differentially stabilized other regions of the binding pocket. The gradient of PPARgamma transactivation cannot be accounted for solely through changes to the dynamics of AF-2. Thus, our understanding of allosteric signaling must be extended beyond the idea of a dynamic helix 12 acting as a molecular switch.
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(as it appears on PubMed at http://www.pubmed.gov), where 17937915 is the PubMed ID number.
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{{ABSTRACT_PUBMED_17937915}}
==About this Structure==
==About this Structure==
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[[Category: Ligand binding protein]]
[[Category: Ligand binding protein]]
[[Category: Protein-ligand complex]]
[[Category: Protein-ligand complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 14:23:09 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:45:13 2008''

Revision as of 05:45, 29 July 2008

Image:2q59.png

Template:STRUCTURE 2q59

Crystal Structure of PPARgamma LBD bound to full agonist MRL20

Template:ABSTRACT PUBMED 17937915

About this Structure

2Q59 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Partial agonists activate PPARgamma using a helix 12 independent mechanism., Bruning JB, Chalmers MJ, Prasad S, Busby SA, Kamenecka TM, He Y, Nettles KW, Griffin PR, Structure. 2007 Oct;15(10):1258-71. PMID:17937915

Page seeded by OCA on Tue Jul 29 08:45:13 2008

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