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Glucose-Dependent Insulinotropic Receptor/GIPR bound with Tirzepatide

1 Introduction
2 Function
- 2.1 Tirzepatide
3 Disease
4 Relevance
5 Structural highlights
- 5.1 Active Site
6 References
7 Student Contributors

Introduction

GIP-R is a receptor that binds glucose within many different cells.

Figure 1: Main Structure of the Glucose Depending Insulinotropic Receptor (GIP-R).

Function

The GIP receptor helps facilitate movement of glucose within a cell. ^[1].

Tirzepatide

Tirzepatide has been used as a treatment for Type 2 diabetes. It has 39 total residues in the structure.

Disease

Diabetes is very bad for you^[2].

Relevance

Structural highlights

Active Site

Main binding domains between tirzepatide and the GIP receptor would contain an arginine 190 and glutamine 220 residues to facilitate binding of the ligand. One key difference found was a point mutation at position 7 between an Isoleucine and Threonine ^[1], which would result in a higher affinity for the tirzepatide molecule binding onto the receptor than the ligand.

Figure 2: Key difference between GIP ligand and Tirzepatide at position 7. Ile7 is in pink (ligand), and Thr7 is in green (tirzepatide).

References

↑ ^1.0 ^1.1 Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW. Structural determinants of dual incretin receptor agonism by tirzepatide. Proc Natl Acad Sci U S A. 2022 Mar 29;119(13):e2116506119. PMID:35333651 doi:10.1073/pnas.2116506119
↑ Ransey E, Paredes E, Dey SK, Das SR, Heroux A, Macbeth MR. Crystal structure of the Entamoeba histolytica RNA lariat debranching enzyme EhDbr1 reveals a catalytic Zn(2+) /Mn(2+) heterobinucleation. FEBS Lett. 2017 Jul;591(13):2003-2010. doi: 10.1002/1873-3468.12677. Epub 2017, Jun 14. PMID:28504306 doi:http://dx.doi.org/10.1002/1873-3468.12677

Student Contributors

SaraKathryn Kalkhoff Camille Gaudet

Proteopedia Page Contributors and Editors (what is this?)

SaraKathryn Kalkhoff

Retrieved from "http://52.214.119.220/wiki/index.php/User:SaraKathryn_Kalkhoff/Sandbox_1"

@@ Line 3: / Line 3: @@
 == Introduction ==
+[https://www.sciencedirect.com/topics/medicine-and-dentistry/gastric-inhibitory-polypeptide GIP-R is a receptor that binds glucose within many different cells.]
+[[Image:Gip.png|300px|right|thumb|Figure 1: Main Structure of the Glucose Depending Insulinotropic Receptor (GIP-R).]]
-[[Image:Gip.png|300px|right|thumb|Figure 1: Main Structure of the Glucose Depending Insulinotropic Receptor (GIP-R).]]
-[https://www.sciencedirect.com/topics/medicine-and-dentistry/gastric-inhibitory-polypeptide GIP-R is a receptor that binds glucose within many different cells.]
 == Function ==
 The GIP receptor helps facilitate movement of glucose within a cell. <ref name='Sun'>PMID:35333651</ref>.
@@ Line 18: / Line 18: @@
 <scene name='10/1037492/Gip_tirz/2'>Main scene of Tirzepatide bound to the GIP receptor. </scene>
 === Active Site ===
+Main binding domains between tirzepatide and the GIP receptor would contain an arginine 190 and glutamine 220 residues to facilitate binding of the ligand. One key difference found was a point mutation at position 7 between an Isoleucine and Threonine <ref name='Sun'>PMID:35333651</ref>, which would result in a higher affinity for the tirzepatide molecule binding onto the receptor than the ligand.
+[[Image:i7_vs_t7.png|300px|left|thumb|Figure 2: Key difference between GIP ligand and Tirzepatide at position 7. Ile7 is in pink (ligand), and Thr7 is in green (tirzepatide).]]
 == References ==
 <references/>