Sandbox Reserved 1170: Difference between revisions
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=== Binding Sites === | === Binding Sites === | ||
[[Image:4phuBind2.png|200 px|right|thumb|Figure 1. Second proposed binding site of hGPR40.]] | [[Image:4phuBind2.png|200 px|right|thumb|Figure 1. Second proposed binding site of hGPR40.]] | ||
[[Image:4phubind3.png|200 px|right|thumb|Figure 2. Third proposed binding site of hGPR40.]][http://metislabs.com/radioligand-binding-assays Radioligand binding studies] identified multiple binding sites in hGPR40. [https://en.wikipedia.org/wiki/Agonist Full agonists] and [https://en.wikipedia.org/wiki/Partial_agonist partial agonists] were shown to bind in separate sites with positive cooperativity<ref name="Lin">PMID:22859723</ref> | [[Image:4phubind3.png|200 px|right|thumb|Figure 2. Third proposed binding site of hGPR40.]][http://metislabs.com/radioligand-binding-assays Radioligand binding studies] identified multiple binding sites in hGPR40. [https://en.wikipedia.org/wiki/Agonist Full agonists] and [https://en.wikipedia.org/wiki/Partial_agonist partial agonists] were shown to bind in separate sites with positive cooperativity.<ref name="Lin">PMID:22859723</ref> The <scene name='72/721542/Tak_binding_site/3'>binding site for the partial agonist TAK-875</scene> has been identified, but other binding sites were hypothesized. TAK-875 binds between transmembrane helices 3, 4, and 5 and underneath ECL2. By visual inspection, a second possible binding site was proposed between transmembrane helices 3, 4, and 5 on the intracellular side of the transmembrane helices. Also by visual inspection, a third possible binding site was proposed between transmembrane helices 1, 2, and 7 on the extracellular side of hGPR40, close to the TAK-875 binding site.<ref name="Srivastava"/> | ||
=== Charge Network === | === Charge Network === | ||
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=== ECL2 === | === ECL2 === | ||
Although it may be different in many ways, hGPR40 is similar to most G protein coupled receptors because it contains a highly conserved hairpin loop. This extracellular loop (<scene name='72/721541/Ecl2/2'>ECL2</scene>), is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] and serves an important role in the protein. In hGPR40, ECL2 has two sections: a beta sheet and an auxiliary loop. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] (shown in cyan) spans helices 4 and 5. The ECL2 of hGPR40 differs from that of other proteins because it contains an auxiliary loop (magenta) of 13 extra residues. The entire extracellular loop has low mobility and flexibility | Although it may be different in many ways, hGPR40 is similar to most G protein coupled receptors because it contains a highly conserved hairpin loop. This extracellular loop (<scene name='72/721541/Ecl2/2'>ECL2</scene>), is accompanied by a [https://en.wikibooks.org/wiki/Structural_Biochemistry/Chemical_Bonding/_Disulfide_bonds disulfide bond] and serves an important role in the protein. In hGPR40, ECL2 has two sections: a beta sheet and an auxiliary loop. The [https://en.wikipedia.org/wiki/Beta_sheet beta sheet] (shown in cyan) spans helices 4 and 5. The ECL2 of hGPR40 differs from that of other proteins because it contains an auxiliary loop (magenta) of 13 extra residues. The entire extracellular loop has low mobility and flexibility which allows it to act as a cap for the binding pocket. The only exception to the low flexibility is the tip of the auxiliary loop, which corresponds to residues Asp 152-Asn 155. This area of greater mobility allows for substrates to enter the binding site.<ref name="Srivastava"/> | ||
== Function == | == Function == | ||
