3LNK

Structure of BACE bound to SCH743813

Summary for 3LNK

• Entry DOI: 10.2210/pdb3lnk/pdb
• Descriptor: Beta-secretase 1, N'-{(1S,2S)-1-(3,5-difluorobenzyl)-2-hydroxy-2-[(2R)-4-(phenylcarbonyl)piperazin-2-yl]ethyl}-5-methyl-N,N-dipropylbenzene-1,3-dicarboxamide, L(+)-TARTARIC ACID, ... (4 entities in total)
• Functional Keywords: alzheimer's, bace1, alternative splicing, aspartyl protease, disulfide bond, endoplasmic reticulum, endosome, glycoprotein, golgi apparatus, 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: 2
• Total formula weight: 89588.89

Authors

Orth, P.,Cumming, J. (deposition date: 2010-02-02, release date: 2010-04-14, Last modification date: 2024-11-06)

Primary citation

Cumming, J.,Babu, S.,Huang, Y.,Carrol, C.,Chen, X.,Favreau, L.,Greenlee, W.,Guo, T.,Kennedy, M.,Kuvelkar, R.,Le, T.,Li, G.,McHugh, N.,Orth, P.,Ozgur, L.,Parker, E.,Saionz, K.,Stamford, A.,Strickland, C.,Tadesse, D.,Voigt, J.,Zhang, L.,Zhang, Q.
Piperazine sulfonamide BACE1 inhibitors: design, synthesis, and in vivo characterization.
Bioorg.Med.Chem.Lett., 20:2837-2842, 2010

PubMed Abstract: With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2' sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Abeta(40) in transgenic mice with a single subcutaneous dose.

PubMed: 20347593
DOI: 10.1016/j.bmcl.2010.03.050

Experimental method

X-RAY DIFFRACTION (1.8 Å)