THE GASTRIC ACID PUMP AS A TARGET FOR ULCER TREATMENT

胃酸泵作为溃疡治疗的目标

• 批准号: 6589241
• 负责人: George Sachs
• 金额: $ 0.61万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6589241
• 关键词: antiulcer drug; benzimidazole analog; binding sites; chemical models; enzyme inhibitors; enzyme mechanism; enzyme structure; gastric acid; hydrogen potassium exchanging ATPase; hydrogen transport; molecular dynamics; pharmacokinetics

This is a new application from an established investigator to investigate structure function relationships of the H+,K+ ATPase. This PI proposes to investigate a new class of acid suppressant medication, imidazo-1,2alpha-pyridnes, which are non-covalent inhibitors of the enzyme. The potential binding sites of SCH28080 and other imidazo-pyridines will be investigated by kinetic measurements in cells transfected with the H+,K+ ATPase and mutated enzyme. Specific membrane segments involved in recognition of this class of inhibitors will be identified. Models will largely rely on the recently identified crystal structure of sr Ca ATPase and Neurospora H+ ATPases, thus the current proposal will refine the model that currently is proposed and maybe used to generate structure-function data for understanding the ion transport role of H+,K+ ATPase and its regulation by this new class of acid suppressant drugs.

这是一家知名调查员提出的新申请 研究H+，K+ATPase的结构和功能关系。这个PI 建议研究一种新型的抑酸药物， 咪唑-1，2-α-吡啶，这是该酶的非共价抑制剂。这个 SCH28080和其他咪唑并吡啶的潜在结合部位将是 H~+，K~+-ATPase转基因细胞的动力学研究 和突变的酶。参与识别这一过程的特定膜片段 将确定抑制剂的类别。模型将在很大程度上依赖于 新近鉴定的锶钙ATPase和脉孢子虫H+的晶体结构 ATPase，因此当前的提案将完善目前的模型 提出并可用于生成用于理解的结构-功能数据 H~+，K~+-ATPase的离子转运作用及其调节 抑酸药物。