3H0B

Discovery of aminoheterocycles as a novel beta-secretase inhibitor class

Summary for 3H0B

• Entry DOI: 10.2210/pdb3h0b/pdb
• Descriptor: Beta-secretase 1, 4-[(1S)-1-(3-fluoro-4-methoxyphenyl)-2-(2-methoxy-5-nitrophenyl)ethyl]-1H-imidazol-2-amine (3 entities in total)
• Functional Keywords: aspartyl protease, alternative splicing, disulfide bond, glycoprotein, hydrolase, membrane, polymorphism, protease, transmembrane, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 136875.80

Authors

Allison, T.J. (deposition date: 2009-04-08, release date: 2009-07-07, Last modification date: 2024-10-30)

Primary citation

Stachel, S.J.,Coburn, C.A.,Rush, D.,Jones, K.L.,Zhu, H.,Rajapakse, H.,Graham, S.L.,Simon, A.,Katharine Holloway, M.,Allison, T.J.,Munshi, S.K.,Espeseth, A.S.,Zuck, P.,Colussi, D.,Wolfe, A.,Pietrak, B.L.,Lai, M.T.,Vacca, J.P.
Discovery of aminoheterocycles as a novel beta-secretase inhibitor class: pH dependence on binding activity part 1.
Bioorg.Med.Chem.Lett., 19:2977-2980, 2009

PubMed Abstract: We have developed a novel series of heteroaromatic BACE-1 inhibitors. These inhibitors interact with the enzyme in a unique fashion that allows for potent binding in a non-traditional paradigm. In addition to the elucidation of their binding profile, we have discovered a pH dependent effect on the binding affinity as a result of the intrinsic pK(a) of these inhibitors and the pH of the BACE-1 enzyme binding assay.

PubMed: 19409780
DOI: 10.1016/j.bmcl.2009.04.033

Experimental method

X-RAY DIFFRACTION (2.7 Å)