2QZK

Crystal structure of human Beta Secretase complexed with I21

Summary for 2QZK

• Entry DOI: 10.2210/pdb2qzk/pdb
• Related: 2QZL
• Descriptor: Beta-secretase 1, 2-[(5R)-5-amino-5-methyl-4,16-dioxo-14-phenyl-3-oxa-15-azatricyclo[15.3.1.1~7,11~]docosa-1(21),7(22),8,10,12,14,17,19-octaen-19-yl]benzonitrile (3 entities in total)
• Functional Keywords: aspartyl protease, bace, alternative splicing, glycoprotein, hydrolase, membrane, transmembrane, zymogen
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 45648.35

Authors

Munshi, S. (deposition date: 2007-08-16, release date: 2008-04-29, Last modification date: 2024-10-30)

Primary citation

Moore, K.P.,Zhu, H.,Rajapakse, H.A.,McGaughey, G.B.,Colussi, D.,Price, E.A.,Sankaranarayanan, S.,Simon, A.J.,Pudvah, N.T.,Hochman, J.H.,Allison, T.,Munshi, S.K.,Graham, S.L.,Vacca, J.P.,Nantermet, P.G.
Strategies toward improving the brain penetration of macrocyclic tertiary carbinamine BACE-1 inhibitors.
Bioorg.Med.Chem.Lett., 17:5831-5835, 2007

PubMed Abstract: This letter describes replacements for the P3 amide moiety present in previously reported tertiary carbinamine macrolactones. Although P-gp efflux issues associated with these amide-macrolactones were solved and full brain penetration was measured in one case, potency was compromised in the process.

PubMed: 17827011
DOI: 10.1016/j.bmcl.2007.08.040

Experimental method

X-RAY DIFFRACTION (1.8 Å)