2q61: Difference between revisions
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[[Image:2q61.jpg|left|200px]] | [[Image:2q61.jpg|left|200px]] | ||
'''Crystal Structure of PPARgamma ligand binding domain bound to partial agonist SR145''' | {{Structure | ||
|PDB= 2q61 |SIZE=350|CAPTION= <scene name='initialview01'>2q61</scene>, resolution 2.197Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=SF1:1-BENZYL-5-CHLORO-3-(PHENYLTHIO)-1H-INDOLE-2-CARBOXYLIC ACID'>SF1</scene> | |||
|ACTIVITY= | |||
|GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''Crystal Structure of PPARgamma ligand binding domain bound to partial agonist SR145''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2Q61 is a [ | 2Q61 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q61 OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/17937915 17937915] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:22:06 2008'' | ||
Revision as of 19:22, 20 March 2008
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| , resolution 2.197Å | |||||||
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| Ligands: | |||||||
| Gene: | PPARG, NR1C3 (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of PPARgamma ligand binding domain bound to partial agonist SR145
OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[601487], Diabetes mellitus, insulin-resistant, with acanthosis nigricans and hypertension OMIM:[601487], Glioblastoma, susceptibility to OMIM:[601487], Insulin resistance, severe, digenic OMIM:[601487], Lipodystrophy, familial partial OMIM:[601487], Obesity, resistance to OMIM:[601487], Obesity, severe OMIM:[601487]
About this StructureAbout this Structure
2Q61 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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