演講研討會公告
Crystal structures of the gastric proton pump – molecular mechanisms for the drug binding, H+ extrusion and K+ counter-transport
2019-12-12 09:30 ~ 2019-12-12 10:30
地點: 生化所209室
主講人: Dr. Kazuhiro Abe
主講人背景: 日本名古屋大學細胞與結構生理學研究所副教授
主講人網站: http://www.ps.nagoya-u.ac.jp/en/teaching_staff/kazuhiro-abe/
演講主持人: 徐尚德副研究員
演講摘要:
The gastric proton pump, H+,K+-ATPase is a membrane protein (P-type ATPase) responsible for acidifying the gastric juice up to pH 1, and is thus an important drug target for treating gastric acid-related diseases. I will present the crystal structures of the H+,K+-ATPase in complex with two acid blockers in the luminal-open E2P state. These drugs have partially overlapped, but clearly distinguishable, binding modes, which are defined in the middle of a conduit running from the gastric lumen to the cation-binding site. The crystal structures also revealed the unusual configuration of the cation-binding site that enables the extrusion of a single proton into the pH1 solution of the stomach. We also show crystal structures of E2-P transition state, in which the counter-transporting K+ is occluded. We found a single K+ bound to the cation-binding site of H+,K+-ATPase, indicating an exchange of 1H+/1K+ per hydrolysis of one ATP molecule. The structural and biochemical analysis establishes how the gastric pump overcomes the energetic challenge to generate an H+ gradient of more than a million-fold - the highest cation gradient known in any mammalian tissue – across the membrane. -Dr. Kazuhiro Abe
洽詢人員: 劉小姐
洽詢電話: 02-27855696#2061
洽詢信箱: liukchun@gate.sinica.edu.tw