ATP4A gene regulatory network for fine-tuning of proton pump and ion channels

摘要

The ATP4A encodes a subunit of H~+, K~+-ATPase that contains catalytic sites of the enzyme forming pores through cell membrane which allows the ion transport. H~+, K~+-ATPase is a membrane bound P-type ATPase enzyme which is found on the surface of parietal cells and uses the energy derived from each cycle of ATP hydrolysis that can help in exchanging ions (H~+, K~+ and CP) across the cell membrane secreting acid into the gastric lumen. The 3-D model of ot-subunit of H~+, K~+-ATPase was generated byhomology modeling. It was. evaluated and validated on the basis of free energies and amino acid residues. The inhibitor binding amino acid active pockets were identified in the 3-D model by molecular docking. The two drugs Omeprazole and Rabeprazole werefound more potent interactions with generated model of a-subunit of H~+, K~+-ATPase on the basis of their affinity betweendrug-protein interactions. We have generated ATP4A gene regulatory networks for interactions with other proteins which involved in regulation that can help in fine-tuning of proton pump and ion channels. These findings provide a new dimension for discovery and development of proton pump inhibitors and gene regulation of the ATPase. It can be helpful in better understanding of human physiology and also using synthetic biology strategy for reprogramming of parietal cells for control of gastric ulcers.