2q61: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2q61 |SIZE=350|CAPTION= <scene name='initialview01'>2q61</scene>, resolution 2.197Å | |PDB= 2q61 |SIZE=350|CAPTION= <scene name='initialview01'>2q61</scene>, resolution 2.197Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=SF1:1-BENZYL-5-CHLORO-3-(PHENYLTHIO)-1H-INDOLE-2-CARBOXYLIC ACID'>SF1</scene> | |LIGAND= <scene name='pdbligand=SF1:1-BENZYL-5-CHLORO-3-(PHENYLTHIO)-1H-INDOLE-2-CARBOXYLIC+ACID'>SF1</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |GENE= PPARG, NR1C3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2q59|2Q59]], [[2q5p|2Q5P]], [[2q5s|2Q5S]], [[2q6r|2Q6R]], [[2q6s|2Q6S]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2q61 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q61 OCA], [http://www.ebi.ac.uk/pdbsum/2q61 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2q61 RCSB]</span> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
==About this Structure== | ==About this Structure== | ||
| Line 27: | Line 27: | ||
[[Category: Bruning, J B.]] | [[Category: Bruning, J B.]] | ||
[[Category: Nettles, K W.]] | [[Category: Nettles, K W.]] | ||
[[Category: ligand binding protein]] | [[Category: ligand binding protein]] | ||
[[Category: protein-ligand complex]] | [[Category: protein-ligand complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:45:11 2008'' | ||
