2OAH

Crystal Structure of Human Beta Secretase Complexed with inhibitor

Summary for 2OAH

• Entry DOI: 10.2210/pdb2oah/pdb
• Descriptor: Beta-secretase 1, N-[(1S,2S)-2-AMINO-1-(3-THIENYLMETHYL)HEXYL]-2-({[(1S,2S)-2-METHYLCYCLOPROPYL]METHYL}AMINO)-6-[METHYL(METHYLSULFONYL)AMINO]ISONICOTINAMIDE (3 entities in total)
• Functional Keywords: aspartyl protease, bace, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 1
• Total formula weight: 45630.46

Authors

Munshi, S. (deposition date: 2006-12-15, release date: 2007-08-14, Last modification date: 2024-10-30)

Primary citation

Stauffer, S.R.,Stanton, M.G.,Gregro, A.R.,Steinbeiser, M.A.,Shaffer, J.R.,Nantermet, P.G.,Barrow, J.C.,Rittle, K.E.,Collusi, D.,Espeseth, A.S.,Lai, M.T.,Pietrak, B.L.,Holloway, M.K.,McGaughey, G.B.,Munshi, S.K.,Hochman, J.H.,Simon, A.J.,Selnick, H.G.,Graham, S.L.,Vacca, J.P.
Discovery and SAR of isonicotinamide BACE-1 inhibitors that bind beta-secretase in a N-terminal 10s-loop down conformation.
Bioorg.Med.Chem.Lett., 17:1788-1792, 2007

PubMed Abstract: A series of low-molecular weight 2,6-diamino-isonicotinamide BACE-1 inhibitors containing an amine transition-state isostere were synthesized and shown to be highly potent in both enzymatic and cell-based assays. These inhibitors contain a trans-S,S-methyl cyclopropane P(3) which bind BACE-1 in a 10s-loop down conformation giving rise to highly potent compounds with favorable molecular weight and moderate to high susceptibility to P-glycoprotein (P-gp) efflux.

PubMed: 17257835
DOI: 10.1016/j.bmcl.2006.12.051

Experimental method

X-RAY DIFFRACTION (1.8 Å)