6JB3

Structure of SUR1 subunit bound with repaglinide

Summary for 6JB3

• Entry DOI: 10.2210/pdb6jb3/pdb
• EMDB information: 9788
• Descriptor: ATP-binding cassette sub-family C member 8 isoform X2, Repaglinide, Digitonin (3 entities in total)
• Functional Keywords: katp, channel, repaglinide, kir, abc transporter, sur, membrane protein, diabetes, insulin secretagogue
• Biological source: Mesocricetus auratus (Golden hamster)
• Total number of polymer chains: 1
• Total formula weight: 178977.41

Authors

Chen, L.,Ding, D.,Wang, M.,Wu, J.-X.,Kang, Y. (deposition date: 2019-01-25, release date: 2019-05-22, Last modification date: 2024-05-29)

Primary citation

Ding, D.,Wang, M.,Wu, J.X.,Kang, Y.,Chen, L.
The Structural Basis for the Binding of Repaglinide to the Pancreatic KATPChannel.
Cell Rep, 27:1848-1857.e4, 2019

PubMed Abstract: 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 (K). However, the mechanisms by which RPG binds to the K channel are poorly understood. Here, we describe two cryo-EM structures: the pancreatic K channel in complex with inhibitory RPG and adenosine-5'-(γ-thio)-triphosphate (ATPγS) at 3.3 Å 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.

PubMed: 31067468
DOI: 10.1016/j.celrep.2019.04.050

Experimental method

ELECTRON MICROSCOPY (3.53 Å)