Sandbox Reserved 1170: Difference between revisions

Human G-protein coupled receptor 40 (hGPR40) is a seven helical transmembrane domain receptor for long-chain free fatty acids that stimulates [[insulin]] secretion.<ref name="Srivastava">PMID:25043059</ref> This [http://www.britannica.com/science/enzyme enzyme] is primarily located in the [https://en.wikipedia.org/wiki/Beta_cell pancreatic β-cells] in the [https://en.wikipedia.org/wiki/Pancreatic_islets islets of Langerhans], and as such, it has become a target for potential [http://www.diabetes.org/living-with-diabetes/treatment-and-care/ Type II Diabetes treatments].<ref name="Kebede">PMID:22308370</ref> Activation of hGPR40 has been shown to both stimulate insulin secretion and decrease glucose concentration.<ref name="Ma">PMID:26620255</ref> GPR40 is a member of a group of homologous [[GPCRs]] all located on chromosome 19q13.1 including GPR41, 42, and 43.<ref name="Burant">PMID:23882043</ref>

[[Image:4phuBind2.png|200 px|right|thumb|Figure 1. Second proposed binding site of GPR40.]]

[[Image:4phubind3.png|200 px|right|thumb|Figure 2. Third proposed binding site of GPR40.]]Radioligand binding studies identified multiple binding sites in hGPR40. Full agonists and 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"/>.