This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Recombinant human beta-secretase (BACE)crystal structures in complex with inhibitorsBeta-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)
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