The cryo-EM structure of gastric H⁺,K⁺-ATPase with bound BYK99, a high-affinity member of K⁺-competitive, imidazo[1,2-a]pyridine inhibitors.

ABSTRACT: The gastric proton pump H⁺,K⁺-ATPase acidifies the gastric lumen, and thus its inhibitors, including the imidazo[1,2-a]pyridine class of K⁺-competitive acid blockers (P-CABs), have potential application as acid-suppressing drugs. We determined the electron crystallographic structure of H⁺,K⁺-ATPase at 6.5 Å resolution in the E2P state with bound BYK99, a potent P-CAB with a restricted ring structure. The BYK99 bound structure has an almost identical profile to that of a previously determined structure with bound SCH28080, the original P-CAB prototype, but is significantly different from the previously reported P-CAB-free form, illustrating a common conformational change is required for P-CAB binding. The shared conformational changes i

SUBMITTER: Abe K 

PROVIDER: S-EPMC5529566 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature