2NTR

Crystal structure of Human Bace-1 bound to inhibitor

Summary for 2NTR

• Entry DOI: 10.2210/pdb2ntr/pdb
• Related: 1TQF 2B8V 2IRZ 2IS0
• Descriptor: Beta-secretase 1, (2R)-2-(5-{3-chloro-6-((2-methoxyethyl){[(1S,2S)-2-methylcyclopropyl]methyl}amino)-2-[methyl(methylsulfonyl)amino]pyrid in-4-yl}-1,3,4-oxadiazol-2-yl)-1-phenylpropan-2-amine (3 entities in total)
• Functional Keywords: bace, aspartyl protease, 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: 45685.86

Authors

Munshi, S. (deposition date: 2006-11-08, release date: 2007-11-13, Last modification date: 2024-10-30)

Primary citation

McGaughey, G.B.,Colussi, D.,Graham, S.L.,Lai, M.T.,Munshi, S.K.,Nantermet, P.G.,Pietrak, B.,Rajapakse, H.A.,Selnick, H.G.,Stauffer, S.R.,Holloway, M.K.
Beta-secretase (BACE-1) inhibitors: accounting for 10s loop flexibility using rigid active sites.
Bioorg.Med.Chem.Lett., 17:1117-1121, 2007

PubMed Abstract: BACE-1 is a flexible enzyme with experimentally determined motion in the flap region, the catalytic aspartates, and the 10s loop. Four in-house crystallographically determined complexes of tertiary carbinamine inhibitors revealed 10s loop motion in the S(3) pocket. These X-ray structures were used to correlate K(i) values, which span over five orders of magnitude, with the calculated interaction energy, using the Merck Molecular Force Field for a series of 19 tertiary carbinamine inhibitors.

PubMed: 17112725
DOI: 10.1016/j.bmcl.2006.11.003

Experimental method

X-RAY DIFFRACTION (1.8 Å)