A research group led by Associate Professor Kazuhiro Abe and Visiting Professor Yoshinori Fujiyoshi of the Center for Cell Physiology, Nagoya University / Graduate School of Pharmaceutical Sciences will elucidate the structure of the gastric proton pump, which is responsible for gastric acid secretion, which is important for digestion. I succeeded in doing so.
When we ingest food, gastric acid is secreted, and the inside of the stomach becomes highly acidic, pH1.Considering that the inside of the cell is neutral (around pH 7), the pH difference from the inside of the stomach is very large.The question of why a gastric proton pump that creates a strong acid environment inside the stomach can create such a strong acid environment has been an unsolved mystery for more than 40 years.
This time, the research group artificially expressed a gastric proton pump using cultured human-derived cells, and created a three-dimensional crystal using a large amount of gastric proton pump prepared from this, and created a large-scale radiation facility Spring-3. By acquiring diffraction data using the X-ray microfocus beam of the above, we succeeded in elucidating the crystal structure to which the gastric acid inhibitor is bound at the atomic level.It was found that the gastric acid inhibitor completely fits into the ion path of the gastric proton pump and blocks its activity to inhibit its activity.In addition, structural analysis revealed for the first time a mechanism that creates a strong acidic environment inside the stomach, which cannot be achieved by other ion pumps, due to the difference in amino acids and the structure of the ion-bonding sites of the gastric ion pump.
This achievement was published in the online version of the British scientific journal "Nature" dated April 2018, 4 (5:2 am Japan time).
Paper information:[Nature] Crystal structures of the gastric proton pump
