Sandbox Reserved 1170

This is a default text for your page Jacob Applegarth/Sandbox 1. Click above on edit this page to modify. Be careful with the < and > signs.

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

Function

Human GPR40 (hGPR40) is a G-protein coupled receptor that binds free fatty acids to enhance glucose dependent insulin signaling.^[3]

Structure

Like most G-protein coupled receptors, hGPR40 contains seven transmembrane helices. In order obtain a crystallized structure of the protein, four (, , , ) were made to increase expression levels and thermal stability of the protein.^[3]

Charge Network

The importance of these residues for agonist binding was determined by mutagenesis studies. Each of these residues have either a charged or polar R-group that allows them to develop a charge network. This network keeps the residues in a stable, unbound state until exposed to a substrate. When the substrate (an agonist) enters the binding pocket, four of the seven interact directly with the carboxylate moiety of the agonist. In 2007 and 2009 researchers showed the presence of Arg 183 and Arg 258 in the binding pocket ^[4][5] Along with the two Arginine residues, the charge network incorporates two Tyrosine residues.These residues (Tyr 91 and Tyr 240) also stabilize the carboxylate of the agonists. It was further determined that Tyr 240 is epecially important for binding. Mutation of Tyr 240 caused a reduction in the binding affinity of TAK-875 by eight fold and had a significant effect on the Kd of the protein.^[3]

ECl2

Although it may be different in many way, hGPR40 contains a highly conserved hairpin loop motif.

Clinical Relevance

This is a sample scene created with SAT to by Group, and another to make of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.