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Title | Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. |
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Journal, issue, pages | Front Pharmacol, Vol. 13, Page 929684, Year 2022 |
Publish date | Jun 30, 2022 |
Authors | Mengmeng Wang / Jing-Xiang Wu / Lei Chen / |
PubMed Abstract | Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic K channels. However, how mitiglinide binds K channels remains unknown. Here, ...Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic K channels. However, how mitiglinide binds K channels remains unknown. Here, we show the cryo-EM structure of the SUR1 subunit complexed with mitiglinide. The structure reveals that mitiglinide binds inside the common insulin secretagogue-binding site of SUR1, which is surrounded by TM7, TM8, TM16, and TM17. Mitiglinide locks SUR1 in the NBD-separated inward-facing conformation. The detailed structural analysis of the mitiglinide-binding site uncovers the molecular basis of its high selectivity. |
External links | Front Pharmacol / PubMed:35847046 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.21 Å |
Structure data | EMDB-32535, PDB-7wit: |
Chemicals | ChemComp-ATP: ChemComp-9I0: |
Source |
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Keywords | MEMBRANE PROTEIN / SUR1 / KATP / channel / mitiglinide |