User:Adam Davis/Sandbox 1
From Proteopedia
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This is an X-ray crystallography structure, solved at 1.95 Å, which models the region of PPARδ from Gln171 to Tyr441<ref>DOI 10.1371/journal.pone.0033643</ref>. It is composed of <scene name='10/1079455/Helices/1'>twelve alpha helices</scene>, with one small <scene name='10/1079455/Beta_sheet/1'>beta sheet region</scene>. The structure is bound to a synthetic ligand, <scene name='10/1079455/Ligand/2'>GW0742</scene>, which contains a carboxylate group, a thiophenol, a thiazole, and a fluorine substituted phenyl ring. This ligand can be divided into a hydrophilic head group (carboxylate) and a hydrophobic tail (thiophenol, thiazole, phenyl). There is also a glycerol molecule in the structure, which is an artifact of the crystallization process and is not biologically relevant. | This is an X-ray crystallography structure, solved at 1.95 Å, which models the region of PPARδ from Gln171 to Tyr441<ref>DOI 10.1371/journal.pone.0033643</ref>. It is composed of <scene name='10/1079455/Helices/1'>twelve alpha helices</scene>, with one small <scene name='10/1079455/Beta_sheet/1'>beta sheet region</scene>. The structure is bound to a synthetic ligand, <scene name='10/1079455/Ligand/2'>GW0742</scene>, which contains a carboxylate group, a thiophenol, a thiazole, and a fluorine substituted phenyl ring. This ligand can be divided into a hydrophilic head group (carboxylate) and a hydrophobic tail (thiophenol, thiazole, phenyl). There is also a glycerol molecule in the structure, which is an artifact of the crystallization process and is not biologically relevant. | ||
| - | The ligand binding pocket (LBP) is made of <scene name='10/1079455/Armsi_ii_iii/2'>three arms</scene> (arm I residues are green, arm II residues are blue, arm III residues are red), with fifteen residues that contact the ligand. <scene name='10/1079455/Armi/1'>Arm I</scene> | + | The ligand binding pocket (LBP) is made of <scene name='10/1079455/Armsi_ii_iii/2'>three arms</scene> (arm I residues are green, arm II residues are blue, arm III residues are red), with fifteen residues that contact the ligand. <scene name='10/1079455/Armi/1'>Arm I</scene> interacts with the ligand through Phe246, Cys249, His287, Phe291, Ile327, His413, Leu433, and Tyr437. The <scene name='10/1079455/Hydrophilic_head/2'>hydrophilic head</scene> of the ligand interacts via polar contacts with Arm I residues His287, His413, and Tyr437. <scene name='10/1079455/Arm_ii/1'>Arm II</scene>, includes residues Val245, Val305, Val312, Leu317, and Ile 328, while <scene name='10/1079455/Arm_iii/1'>Arm III</scene> includes Leu249 and Thr252. The <scene name='10/1079455/Hydrophobic_tail/2'>hydrophobic tail</scene> of the ligand interacts via nonpolar contacts with residues from all three arms (Phe246, Phe291, His 413, Ile327, Leu433, Cys249, Val245, Val305, Val312, Leu317, Ile328, Thr252, and Leu294). |
| - | Comparing this structure to structures of ligand-bound PPARα and PPARγ, the authors found that <scene name='10/1079455/Val312_ile328/3'>two residues</scene> from Arm II, Val312 and Ile328, are key to the specificity of this ligand for PPARδ. | + | Comparing this structure to structures of ligand-bound PPARα and PPARγ, the authors found that <scene name='10/1079455/Val312_ile328/3'>two LBP residues</scene> from Arm II, Val312 and Ile328, are key to the specificity of this ligand for PPARδ. |
== Function == | == Function == | ||
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| + | Activation of PPARδ improves overall metabolic health. | ||
== Disease == | == Disease == | ||
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== Relevance == | == Relevance == | ||
Revision as of 17:49, 28 April 2025
PPARδ Bound to GW074
Peroxisome proliferator activated receptors are transcription factors.
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References
- ↑ Batista FA, Trivella DB, Bernardes A, Gratieri J, Oliveira PS, Figueira AC, Webb P, Polikarpov I. Structural Insights into Human Peroxisome Proliferator Activated Receptor Delta (PPAR-Delta) Selective Ligand Binding. PLoS One. 2012;7(5):e33643. Epub 2012 May 11. PMID:22606221 doi:10.1371/journal.pone.0033643
