Sandbox Reserved 1165: Difference between revisions

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There are specific amino acid interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> ~~This includes~~ the [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> ~~that~~ serves to hold the helices in the proper orientation for binding. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346~~, also mentioned earlier,~~ hold the conformation together for higher affinity (Figure 3). <ref name="Ligands">PMID: 21542831</ref> Finally, alpha helical structure of the <scene name='72/721535/Opening_orientation/2'>stalk</scene> is required for high affinity conformation. The high affinity conformation of GCGR is the open conformation when glucagon can bind. Without these specific interactions between the residues open conformation is not stabilized and GCGR remains in the closed conformation where glucagon cannot bind. <ref name="Tips">PMID: 23863937</ref>

There are specific amino acid interactions that maximize affinity. This includes the alpha helical structure of the <scene name='72/721535/Opening_orientation/2'>stalk</scene>. The alpha helical structure of the stalk interacts directly with glucagon; when the alpha helix of the stalk is disrupted, the affinity of glucagon for GCGR decreases. Furthermore, there are certain interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> The high affinity conformation of GCGR is the open conformation when glucagon can bind. Without these specific interactions between the residues, open conformation is not stabilized and GCGR remains in the closed conformation where glucagon cannot bind. <ref name="Tips">PMID: 23863937</ref> The [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> serves to hold the helices in the proper orientation for binding and stabilize the open conformation. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346 hold the open conformation together for higher affinity (Figure 4). <ref name="Ligands">PMID: 21542831</ref>

[[Image:Screen Shot 2016-03-29 at 3.24.43 PM.png|(|):|400 px|center|thumb|'''Figure 3: Salt Bridge'''. The non-covalent interactions between residues Glu 406, Arg 173, and Arg 346 form a [https://en.wikipedia.org/wiki/Denticity tridentate] salt bridge. The Glu 406 acts as the central residue in the tridentate salt bridge; Arg 173 and Arg 436 both interact with Glu 406. The salt bridge is located on the intracellular side of the transmembrane helices.]]

[[Image:Screen Shot 2016-03-29 at 3.24.43 PM.png|(|):|400 px|center|thumb|'''Figure 4: Salt Bridge'''. The non-covalent interactions between residues Glu 406, Arg 173, and Arg 346 form a [https://en.wikipedia.org/wiki/Denticity tridentate] salt bridge. The Glu 406 acts as the central residue in the tridentate salt bridge; Arg 173 and Arg 436 both interact with Glu 406. The salt bridge is located on the intracellular side of the transmembrane helices.]]

Sandbox Reserved 1165: Difference between revisions

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Revision as of 23:20, 18 April 2016 view source Sydney Caskey (talk \| contribs) 73 edits No edit summary ← Older edit		Revision as of 23:34, 18 April 2016 view source Sydney Caskey (talk \| contribs) 73 edits No edit summary Newer edit →
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	There are specific amino acid interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> ~~This includes~~ the [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> ~~that~~ serves to hold the helices in the proper orientation for binding. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346~~, also mentioned earlier,~~ hold the conformation together for higher affinity (Figure 3). <ref name="Ligands">PMID: 21542831</ref> Finally, alpha helical structure of the <scene name='72/721535/Opening_orientation/2'>stalk</scene> is required for high affinity conformation. The high affinity conformation of GCGR is the open conformation when glucagon can bind. Without these specific interactions between the residues open conformation is not stabilized and GCGR remains in the closed conformation where glucagon cannot bind. <ref name="Tips">PMID: 23863937</ref>		There are specific amino acid interactions that maximize affinity. This includes the alpha helical structure of the <scene name='72/721535/Opening_orientation/2'>stalk</scene>. The alpha helical structure of the stalk interacts directly with glucagon; when the alpha helix of the stalk is disrupted, the affinity of glucagon for GCGR decreases. Furthermore, there are certain interactions that hold the helices of the 7TM in the conformation that maximizes [http://www.chemicool.com/definition/affinity.html affinity]. <ref name="Ligands">PMID: 21542831</ref> The high affinity conformation of GCGR is the open conformation when glucagon can bind. Without these specific interactions between the residues, open conformation is not stabilized and GCGR remains in the closed conformation where glucagon cannot bind. <ref name="Tips">PMID: 23863937</ref> The [https://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='72/721535/Disulfide_bond_notspin/1'> Cys 294 and Cys 224</scene> serves to hold the helices in the proper orientation for binding and stabilize the open conformation. Additionally, the [https://en.wikipedia.org/wiki/Salt_bridge_%28protein_and_supramolecular%29 salt bridges] between Glu 406, Arg 173, and Arg 346 hold the open conformation together for higher affinity (Figure 4). <ref name="Ligands">PMID: 21542831</ref>


	[[Image:Screen Shot 2016-03-29 at 3.24.43 PM.png\|(\|):\|400 px\|center\|thumb\|'''Figure 3: Salt Bridge'''. The non-covalent interactions between residues Glu 406, Arg 173, and Arg 346 form a [https://en.wikipedia.org/wiki/Denticity tridentate] salt bridge. The Glu 406 acts as the central residue in the tridentate salt bridge; Arg 173 and Arg 436 both interact with Glu 406. The salt bridge is located on the intracellular side of the transmembrane helices.]]		[[Image:Screen Shot 2016-03-29 at 3.24.43 PM.png\|(\|):\|400 px\|center\|thumb\|'''Figure 4: Salt Bridge'''. The non-covalent interactions between residues Glu 406, Arg 173, and Arg 346 form a [https://en.wikipedia.org/wiki/Denticity tridentate] salt bridge. The Glu 406 acts as the central residue in the tridentate salt bridge; Arg 173 and Arg 436 both interact with Glu 406. The salt bridge is located on the intracellular side of the transmembrane helices.]]