User:Mandy Bechman/Sandbox 1: Difference between revisions
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[[Image:TZ_hydrogen_bonds.jpg|350 px|right|thumb|GIPR (pink) and Tirzepatide (dark pink) residue interactions]] | [[Image:TZ_hydrogen_bonds.jpg|350 px|right|thumb|GIPR (pink) and Tirzepatide (dark pink) residue interactions]] | ||
The <scene name='10/1038815/Tirzepatide_active_site/4'>binding site</scene> with Tirzepatide is the same as GIP with the N-term binding to the transmembrane domain and activating cellular signaling.The <scene name='10/1038815/Tirzepatide_residues/7'>residues</scene> are fairly similar just in a different conformations, which is allowing for more hydrogen bonding. In Tirzepatide, the most noticeable conformational change is the Tyrosine 1 (Y1) residue. It is now facing up towards Arginine 190 (R190) where they can now form a new hydrogen bond that was not present in GIP. The more hydrogen bonding there is between molecules, the stronger the binding between the two molecules will be. This can lead to the conclusion that GIPR has a higher binding affinity for Tirzepatide than GIP itself<ref name="Sun"/>. | The <scene name='10/1038815/Tirzepatide_active_site/4'>binding site</scene> with Tirzepatide is the same as GIP with the N-term binding to the transmembrane domain and activating cellular signaling.The <scene name='10/1038815/Tirzepatide_residues/7'>residues</scene> are fairly similar just in a different conformations, which is allowing for more hydrogen bonding. In Tirzepatide, the most noticeable conformational change is the Tyrosine 1 (Y1) residue. It is now facing up towards Arginine 190 (R190) where they can now form a new hydrogen bond that was not present in GIP. The more hydrogen bonding there is between molecules, the stronger the binding between the two molecules will be. This can lead to the conclusion that GIPR has a higher binding affinity for Tirzepatide than GIP itself<ref name="Sun"/>. | ||
=== Isoleucine vs. Threonine === | |||
In GIP there is an Isoleucine present <scene name='10/1038815/Gip_ile7/3'>(I7)</scene>. Isoleucine is a branched residue that is very hydrophobic. This residue is also present in the N-term where the important interactions are occuring. In Tirzepatide, this seventh residue has been changed to a Threonine residue <scene name='10/1038815/Tirzepatide_thr7/3'>(T7)</scene>. Threonine is also a branched residue, but it contains a hydroxyl group making it hydrophilic, allowing it to make hydrogen bonds. Threonine 7 (T7) is also making a hydrogen bone with the Arginine 190 (R190) residue. This extra hydrogen bond in Tirzepatide is also responsible for a higher binding affinity for the drug than GIP itself. | |||
