User:Mandy Bechman/Sandbox 1: Difference between revisions

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=== Isoleucine vs. Threonine ===
=== 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.  
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.  
 
===AIB Mutation===
 
[[Image:AlatoAIB.png|400 px|left|thumb|Structure of alanine converted to AIB.]]
[[Image:AlatoAIB.png|400 px|left|thumb|Structure of alanine converted to AIB.]]
 
In GIP, residue 2 is an <scene name='10/1038867/Alanine_2_-_gip/3'>alanine</scene> but in Tirzepatide, the residue changes to <scene name='10/1038867/Tirzepatide_-_aib/2'>AIB</scene>. Residue 2 is where DPP4 recognizes GIP in order to cleave and inactivate the hormone. When the residue is changed, it is no longer recognized by DPP4 because AIB is a noncoding residue, resulting in continuous signaling to the cell.
 
== Relevance ==
In GIP, the residue 2 is an <scene name='10/1038867/Alanine_2_-_gip/3'>alanine</scene> but in Tirzepatide, the residue changes to <scene name='10/1038867/Tirzepatide_-_aib/2'>AIB</scene>




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