2XFJ

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide

Summary for 2XFJ

• Entry DOI: 10.2210/pdb2xfj/pdb
• Related: 1FKN 1M4H 1PY1 1SGZ 1TQF 1UJJ 1UJK 1W50 1W51 1XN2 1XN3 1XS7 1YM2 1YM4 2B8L 2B8V 2FDP 2VA5 2VA6 2VA7 2VIE 2VIJ 2VIY 2VIZ 2VJ6 2VJ7 2VJ9 2VKM 2VNM 2VNN 2WEZ 2WF0 2WF1 2WF2 2WF3 2WF4 2WJO 2XFI 2XFK
• Descriptor: BETA-SECRETASE 1, N-[(1S,2R)-1-benzyl-3-{[(1S)-2-(cyclohexylamino)-1-methyl-2-oxoethyl]amino}-2-hydroxypropyl]-3-(ethylamino)-5-(2-oxopyrrolidin-1-yl)benzamide (3 entities in total)
• Functional Keywords: zymogen, protease, hydrolase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44325.04

Authors

Clarke, B.,Cutler, L.,Demont, E.,Dingwall, C.,Dunsdon, R.,Hawkins, J.,Howes, C.,Hussain, I.,Maile, G.,Matico, R.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Rowland, P.,Soleil, V.,Smith, K.J.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Wayne, G. (deposition date: 2010-05-24, release date: 2010-07-07, Last modification date: 2024-10-16)

Primary citation

Clarke, B.,Cutler, L.,Demont, E.,Dingwall, C.,Dunsdon, R.,Hawkins, J.,Howes, C.,Hussain, I.,Maile, G.,Matico, R.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Rowland, P.,Soleil, V.,Smith, K.J.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Wayne, G.
Bace-1 Inhibitors Using Novel Edge-to-Face Interaction with Arg-296
Bioorg.Med.Chem.Lett., 20:4639-, 2010

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 a series of potent inhibitors based on an hydroxyethylamine (HEA) transition state mimetic template. These inhibitors interact with the non prime side of the enzyme using a novel edge-to-face interaction with Arg-296.

PubMed: 20579874
DOI: 10.1016/J.BMCL.2010.05.111

Experimental method

X-RAY DIFFRACTION (1.8 Å)