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

• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: peptic ulcer H(+)-K(+)-exchanging ATPase protein structural homology drug design
• 年，卷（期）: 2004,（4）
• 页码范围: 474-479
• 页数: 6页
• 分类号: R9
• 语种: 英文

摘要

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 Ca2+-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-TM 10) 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.