5YLV

Crystal structure of the gastric proton pump complexed with SCH28080

Summary for 5YLV

• Entry DOI: 10.2210/pdb5ylv/pdb
• Descriptor: Potassium-transporting ATPase alpha chain 1, Potassium-transporting ATPase subunit beta, 2-(2-methyl-8-phenylmethoxy-imidazo[1,2-a]pyridin-3-yl)ethanenitrile, ... (9 entities in total)
• Functional Keywords: gastric, proton pump, h+, k+-atpase, p-type atpase, transporter, membrane protein
• Biological source: Sus scrofa (Pig); More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P19156; Cell membrane ; Single-pass type II membrane protein : P18434
• Total number of polymer chains: 2
• Total formula weight: 150525.67

Authors

Abe, K.,Irie, K.,Nakanishi, H.,Fujiyoshi, Y. (deposition date: 2017-10-19, release date: 2018-04-11, Last modification date: 2024-11-20)

Primary citation

Abe, K.,Irie, K.,Nakanishi, H.,Suzuki, H.,Fujiyoshi, Y.
Crystal structures of the gastric proton pump
Nature, 556:214-218, 2018

PubMed Abstract: The gastric proton pump-the H, K-ATPase-is a P-type ATPase responsible for acidifying the gastric juice down to pH 1. This corresponds to a million-fold proton gradient across the membrane of the parietal cell, the steepest known cation gradient of any mammalian tissue. The H, K-ATPase is an important target for drugs that treat gastric acid-related diseases. Here we present crystal structures of the H, K-ATPase in complex with two blockers, vonoprazan and SCH28080, in the luminal-open state, at 2.8 Å resolution. The drugs have partially overlapping but clearly distinct binding modes in the middle of a conduit running from the gastric lumen to the cation-binding site. The crystal structures suggest that the tight configuration at the cation-binding site lowers the pK value of Glu820 sufficiently to enable the release of a proton even into the pH 1 environment of the stomach.

PubMed: 29618813
DOI: 10.1038/s41586-018-0003-8

Experimental method

X-RAY DIFFRACTION (2.79977781895 Å)