Structure of Peptides that Inhibit Pertussis Toxin-Receptor Binding

抑制百日咳毒素受体结合的肽的结构

• 批准号: 9304319
• 负责人: Charles Spangler
• 金额: $ 1.8万
• 依托单位: Northern Illinois University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-15 至 1995-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9304319&HistoricalAwards=false
• 关键词: Structure; Peptides; Inhibit; Pertussis; Toxin

Dr. Spangler proposes to study the molecular basis for recognition of receptor ligands by bacterial toxins, characterizing the amino acid residues and structural conformation of the toxin's receptor- binding site and modeling the receptor-toxin interaction with conformationally restrained peptides. This goal will be accomplished in part by a combination of computer-assisted molecular modeling and experimental binding studies of specific peptide fragments recently shown to inhibit pertussis toxin binding to receptor analogs. To initiate this study and facilitate the molecular dynamics portion of the project, three-dimensional structural information for these peptides will be required, coupled with an experimental determination of the binding characteristics of the peptides. The proposed preliminary study will consist of: (a) peptide structure prediction by computational methods (b) peptide structure solution by NMR methods (c) computer modeling of peptide interaction with receptor analogs (d) experimental verification of the ability of the peptides to bind receptor analogs and to block the binding of the intact toxin %%% The long range goal is to explore protein-ligand interactions and provide a rational basis for understanding and manipulating molecular recognition in both binding functions and protein folding. The techniques and information developed are of value in prediction of receptor structures to aid design of drugs, herbicides or pesticides; antigens in vaccine design; or novel molecules, such as catalytic antibodies and new molecular electronic devices based on proteins, that can be developed by protein engineering to provide a template for catalysis or electron transfer.

斯潘格勒博士建议研究识别的分子基础 受体配体的细菌毒素，表征氨基 毒素受体的酸残基和结构构象 结合位点和模拟受体-毒素相互作用， 构象受限的肽。 这一目标将 部分由计算机辅助的 分子模拟和实验结合研究的具体 最近显示抑制百日咳毒素结合的肽片段 to receptor受体analogs类似物. 启动这项研究并促进 分子动力学部分的项目，三维 需要这些肽的结构信息， 结合特性的实验测定 的肽。 拟议的初步研究将包括： (a)用计算方法预测肽结构 (b)核磁共振肽结构解析 (c)肽与受体相互作用的计算机模拟 类似物 (d)肽的能力的实验验证 以结合受体类似物并阻断受体类似物的结合。 完整毒素 %%% 长期目标是探索蛋白质-配体相互作用， 为理解和操纵提供了理性基础 分子 识别结合功能和蛋白质折叠。 的 所开发的技术和信息在预测 受体结构，以帮助设计药物、除草剂或 杀虫剂;疫苗设计中的抗原;或新分子，如 催化抗体和新的分子电子器件 蛋白质，可以通过蛋白质工程来开发， 催化或电子转移的模板。