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Structural Insights Into the High Selectivity of the Anti-Diabetic Drug Mitiglinide


ABSTRACT: Mitiglinide is a highly selective fast-acting anti-diabetic drug that induces insulin secretion by inhibiting pancreatic KATP channels. However, how mitiglinide binds KATP 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.

SUBMITTER: Wang M 

PROVIDER: S-EPMC9279661 | biostudies-literature |

REPOSITORIES: biostudies-literature

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