3DM6

Beta-secretase 1 complexed with statine-based inhibitor

Summary for 3DM6

• Entry DOI: 10.2210/pdb3dm6/pdb
• Descriptor: Beta-secretase 1, 5-[[(2S)-2-[[(3R,4S)-5-(3,5-difluorophenoxy)-3-hydroxy-4-[[3-(methyl-methylsulfonyl-amino)-5-[[(1R)-1-phenylethyl]carbamoyl]phenyl]carbonylamino]pentanoyl]amino]-3-methyl-butanoyl]amino]benzene-1,3-dicarboxylic acid, ISOPROPYL ALCOHOL, ... (4 entities in total)
• Functional Keywords: bace, beta-secretase, statine, inhibitor, alternative splicing, aspartyl protease, glycoprotein, hydrolase, membrane, protease, transmembrane, zymogen
• Biological source: Homo sapiens (Human)
• Cellular location: Membrane; Single-pass type I membrane protein: P56817
• Total number of polymer chains: 3
• Total formula weight: 139014.22

Authors

Lindberg, J.,Borkakoti, N.,Nystrom, S. (deposition date: 2008-06-30, release date: 2008-12-16, Last modification date: 2024-11-13)

Primary citation

Back, M.,Nyhlen, J.,Kvarnstrom, I.,Appelgren, S.,Borkakoti, N.,Jansson, K.,Lindberg, J.,Nystrom, S.,Hallberg, A.,Rosenquist, S.,Samuelsson, B.
Design, synthesis and SAR of potent statine-based BACE-1 inhibitors: exploration of P1 phenoxy and benzyloxy residues
Bioorg.Med.Chem., 16:9471-9486, 2008

PubMed Abstract: Several BACE-1 inhibitors with low nanomolar level activities, encompassing a statine-based core structure with phenyloxymethyl- and benzyloxymethyl residues in the P1 position, are presented. The novel P1 modification introduced to allow the facile exploration of the S1 binding pocket of BACE-1, delivered highly promising inhibitors.

PubMed: 18842420
DOI: 10.1016/j.bmc.2008.09.041

Experimental method

X-RAY DIFFRACTION (2.6 Å)