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bioRxiv · 10.1101/2022.04.26.489624

Structural insights into the high selectivity of the anti-diabetic drug mitiglinide

Wang, M.·Wu, J.-X.·Chen, L.
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Abstract

Mitiglinide is a highly selective fast-acting anti-diabetic drug that inhibits pancreatic KATP channels to induce insulin secretion. However, how mitiglinide binds KATP channels remains unknown. Here, we show the cryo-EM structure of the SUR1 subunit in complex with mitiglinide. The structure reveals that mitiglinide binds inside the common insulin secretagogue-binding site in the transmembrane domain of SUR1, locking SUR1 in a NBD-separated inward-facing conformation. The detailed structural analysis uncovers the molecular basis of the high selectivity of mitiglinide.

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Wang, M., Wu, J.-X., Chen, L.. 2022-04-28. Structural insights into the high selectivity of the anti-diabetic drug mitiglinide. https://doi.org/10.1101/2022.04.26.489624

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