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

Overview

Journal Front Pharmacol

Date 2022 Jul 18

PMID 35847046

Authors

Mengmeng Wang

Jing-Xiang Wu

Lei Chen

Affiliations

Soon will be listed here.

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, 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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