title: ATP4A gene regulatory network for fine-tuning of proton pump and ion channels.
abstract: The ATP4A encodes α 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 Cl(-)) across the cell membrane secreting acid into the gastric lumen. The 3-D model of α-subunit of H(+), K(+)-ATPase was generated by homology 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 were found more potent interactions with generated model of α-subunit of H(+), K(+)-ATPase on the basis of their affinity between drug-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.
authors.affiliation: Molecular Diagnostics and Biotechnology Laboratory, Division of Crop Protection, Central Institute for Subtropical Horticulture, Rehmankhera, Lucknow, 227107 India ; Division of Biotechnology and Bioinformatics, Biobrainz Life Sciences, Vikas nagar, Lucknow, 226022 India.
authors.forename: Vijai
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, 221005 India ; National Bureau of Fish Genetic Resources, Canal Ring Road, PO-Dilkusha, Lucknow, 226002 India.
authors.forename: Indra
authors.initials: I
authors.lastname: Mani
authors.affiliation: National Bureau of Fish Genetic Resources, Canal Ring Road, PO-Dilkusha, Lucknow, 226002 India.
authors.forename: Dharmendra Kumar
authors.initials: DK
authors.lastname: Chaudhary
keywords: ATP4A gene network; Docking; Gastric ulcer; H+, K+-ATPase; Homology modeling