3DV1

Crystal structure of human beta-secretase in complex with NVP-ARV999

Summary for 3DV1

• Entry DOI: 10.2210/pdb3dv1/pdb
• Related: 3DUY 3DV5
• Descriptor: Beta-secretase 1, (2R,4S)-N-butyl-4-[(2S,5S,7R)-2,7-dimethyl-3,15-dioxo-1,4-diazacyclopentadecan-5-yl]-4-hydroxy-2-methylbutanamide (3 entities in total)
• Functional Keywords: beta-secretase, bace1, memapsin2, aspartic protease, enzyme inhibitor complex, alzheimer's disease, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, transmembrane, zymogen
• Biological source: Homo sapiens
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 135650.90

Authors

Rondeau, J.-M. (deposition date: 2008-07-18, release date: 2009-02-24, Last modification date: 2024-10-16)

Primary citation

Machauer, R.,Laumen, K.,Veenstra, S.,Rondeau, J.M.,Tintelnot-Blomley, M.,Betschart, C.,Jaton, A.L.,Desrayaud, S.,Staufenbiel, M.,Rabe, S.,Paganetti, P.,Neumann, U.
Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.
Bioorg.Med.Chem.Lett., 19:1366-1370, 2009

PubMed Abstract: The macrocyclic peptidic BACE-1 inhibitors 2a-c show moderate enzymatic and cellular activity. By exchange of the hydroxyethylene- to ethanolamine-transition state mimetic the peptidic character was reduced, providing the highly potent and selective inhibitor 3. Variation of the P' moiety resulted in the macrocyclic inhibitor 14. Both macrocycles show inhibition of BACE-1 in the brain of APP51/16 transgenic mice, 3 (NB-544) after intravenous and 14 (NB-533) after oral application.

PubMed: 19195887
DOI: 10.1016/j.bmcl.2009.01.055

Experimental method

X-RAY DIFFRACTION (2.1 Å)