A model of 3D-structure of H+, K+-ATPase catalytic subunit derived by homology modeling.

AIM: To build a model of 3D-structure of H(+), K(+)-ATPase catalytic subunit for theoretical study and anti-ulcer drug design. METHODS: The model was built on the basis of structural data from the Ca(2+)-ATPase. Structurally conserved regions were defined by amino acid sequence comparisons, optimum interconnecting loops were selected from the protein databank, and amino (N)- and carboxyl (C)-terminal ends were generated as random coil structures. Applying molecular mechanics method then minimized the model energy. Molecular dynamics technique was used to do further structural optimization. RESULTS: The model of 3D-structure of H(+), K(+)-ATPase was derived. The model is reasonable according to several validation criteria. There were ten transmembrane helices (TM1-TM10) in the model and inhibitor-binding site was identified on the TM5-8 riched negatively charged residues. CONCLUSION: The 3D-structure model from our study is informative to guide future molecular biology study about H(+), K(+)-ATPase and drug design based on database searching.