User:Adam Davis/Sandbox 1: Difference between revisions

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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).  
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 LBP residues</scene> from Arm II, Val312 and Ile328, are key to the specificity of this ligand for PPARδ.  
Using site-directed mutagenesis to replace LBP amino acids with methionine, 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 ==


PPARs are ligand-activated transcription factors<ref>DOI 10.1371/journal.pone.0033643</ref>. Activation of PPARδ (formerly called PPARβ) improves overall metabolic health.  
PPARs are ligand-activated transcription factors<ref>DOI 10.1016/j.pharmthera.2009.12.001</ref>. Activation of PPARδ (formerly called PPARβ) improves overall metabolic health.


== Disease ==
== Disease ==
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