Structural highlights
Function
A0A1U7R319_MESAU
Publication Abstract from PubMed
Repaglinide (RPG) is a short-acting insulin secretagogue widely prescribed for the treatment of type 2 diabetes. It boosts insulin secretion by inhibiting the pancreatic ATP-sensitive potassium channel (KATP). However, the mechanisms by which RPG binds to the KATP channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic KATP channel in complex with inhibitory RPG and adenosine-5'-(gamma-thio)-triphosphate (ATPgammaS) at 3.3 A and a medium-resolution structure of a RPG-bound mini SUR1 protein in which the N terminus of the inward-rectifying potassium channel 6.1 (Kir6.1) is fused to the ABC transporter module of the sulfonylurea receptor 1 (SUR1). These structures reveal the binding site of RPG in the SUR1 subunit. Furthermore, the high-resolution structure reveals the complex architecture of the ATP binding site, which is formed by both Kir6.2 and SUR1 subunits, and the domain-domain interaction interfaces.
The Structural Basis for the Binding of Repaglinide to the Pancreatic KATP Channel.,Ding D, Wang M, Wu JX, Kang Y, Chen L Cell Rep. 2019 May 7;27(6):1848-1857.e4. doi: 10.1016/j.celrep.2019.04.050. PMID:31067468[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ding D, Wang M, Wu JX, Kang Y, Chen L. The Structural Basis for the Binding of Repaglinide to the Pancreatic KATP Channel. Cell Rep. 2019 May 7;27(6):1848-1857.e4. doi: 10.1016/j.celrep.2019.04.050. PMID:31067468 doi:http://dx.doi.org/10.1016/j.celrep.2019.04.050
