2VIY

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(pentylsulfonyl)benzamide

Summary for 2VIY

• Entry DOI: 10.2210/pdb2viy/pdb
• Related: 1FKN 1M4H 1PY1 1SGZ 1TQF 1UJJ 1UJK 1W50 1W51 1XN2 1XN3 1XS7 1YM2 1YM4 2B8L 2B8V 2VA5 2VA6 2VA7 2VIE 2VIJ 2VIZ
• Descriptor: BETA-SECRETASE 1, N-[(1S,2R)-1-benzyl-3-{[(1S)-2-(cyclohexylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl]-3-(pentylsulfonyl)benzamide (3 entities in total)
• Functional Keywords: alternative splicing, beta-site app cleaving enzyme, beta-secretase, aspartyl protease, asp-2, bace-1, zymogen, protease, membrane, hydrolase, memapsin-2, glycoprotein, transmembrane
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44333.08

Authors

Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Hawkins, J.,Hussain, I.,MacPherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Soleil, V.,Smith, K.,Stanway, S.,Stemp, G.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G. (deposition date: 2007-12-06, release date: 2008-01-29, Last modification date: 2019-05-15)

Primary citation

Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Hawkins, J.,Hussain, I.,Macpherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Soleil, V.,Smith, K.,Stanway, S.,Stemp, G.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G.
Bace-1 Inhibitors Part 1: Identification of Novel Hydroxy Ethylamines (Heas).
Bioorg.Med.Chem.Lett., 18:1011-, 2008

PubMed Abstract: Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.

PubMed: 18171614
DOI: 10.1016/J.BMCL.2007.12.017

Experimental method

X-RAY DIFFRACTION (1.82 Å)