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-Structure paper
タイトル | Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide. |
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ジャーナル・号・ページ | Front Pharmacol, Vol. 13, Page 929684, Year 2022 |
掲載日 | 2022年6月30日 |
![]() | Mengmeng Wang / Jing-Xiang Wu / Lei Chen / ![]() |
PubMed 要旨 | 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. |
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手法 | EM (単粒子) |
解像度 | 3.21 Å |
構造データ | EMDB-32535, PDB-7wit: |
化合物 | ![]() ChemComp-ATP: ![]() ChemComp-9I0: |
由来 |
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![]() | MEMBRANE PROTEIN / SUR1 / KATP / channel / mitiglinide |