BACE X-RAY STRUCTURE STUDIES

BACE X 射线结构研究

• 批准号: 7725997
• 负责人: Z HELEN WU
• 金额: $ 0.39万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725997
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Aspartic Endopeptidases; Binding; Biochemistry; Cleaved cell; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Escherichia coli; Funding; Goals; Grant; Housing; Human; Institution; KLK3 gene; Membrane; Nature; Proteins; Recombinants; Research; Research Personnel; Resources; Roentgen Rays; Science; Source; Structure; United States National Institutes of Health; beamline; beta secretase; drug development; drug discovery; inhibitor/antagonist; secretase

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Recombinant human beta-secretase (BACE)crystal structures in complex with inhibitors Beta-Secretase (BACE) is a membrane-bound aspartyl protease that cleaves the amyloid precursor protein to generate the N-terminus of the amyloid beta (ab) peptide. b-Secretase has been implicated to be an excellent target for anti-amyloid therapy for the treatment of Alzheimer?s disease. Finding inhibitors of b-secretase is one of the major goals of Alzheimer?s disease drug development. The recombinant BACE proteins we used were expressed in E coli and subsequently refolded and purified to grow co-crystals with in-house inhibitors. The crystals will be studied using X-ray beamlines, like those at APS, to get diffraction data, which will be analyzed for structural information to enhance our drug discovery efforts. References 1. Hardy, J. and Selkoe, D.J., Science, 297, 353-356 (2002). 2. Shearman, M.S., et al., Biochemistry, 39, 8698-8704 (2000). 3. Li, Y-M., et al., Proc. Nat. Acad. Sci. USA, 97, 6138-6143 (2000). 4. Li, Y-M., et al., Nature, 405, 689-694 (2000). 5. Tian G., et al., J. Biol. Chem., 277, 31499-31505 (2002). 6. Hong, L., et al., Science 290, 150-153(2000)

这个子项目是众多研究子项目之一