2VIJ

Human BACE-1 in complex with 3-(1,1-dioxidotetrahydro-2H-1,2-thiazin- 2-yl)-5-(ethylamino)-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(1,2,3,4- tetrahydro-1-naphthalenylamino)propyl)benzamide

2VIJ の概要

• エントリーDOI: 10.2210/pdb2vij/pdb
• 関連するPDBエントリー: 1FKN 1M4H 1PY1 1SGZ 1TQF 1UJJ 1UJK 1W50 1W51 1XN2 1XN3 1XS7 1YM2 1YM4 2B8L 2B8V 2VA5 2VA6 2VA7 2VIE
• 分子名称: BETA-SECRETASE 1, N-{(1S,2R)-1-benzyl-2-hydroxy-3-[(1S)-1,2,3,4-tetrahydronaphthalen-1-ylamino]propyl}-3-(1,1-dioxido-1,2-thiazinan-2-yl)-5-(ethylamino)benzamide (3 entities in total)
• 機能のキーワード: alternative splicing, beta-site app cleaving enzyme, beta-secretase, aspartyl protease, asp-2, bace-1, zymogen, protease, membrane, hydrolase, memapsin-2, glycoprotein, transmembrane
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44942.86

構造登録者

Beswick, P.,Charrier, N.,Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Gleave, R.,Hawkins, J.,Hussain, I.,Johnson, C.N.,Macpherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Skidmore, J.,Soleil, V.,Smith, K.J.,Stanway, S.,Stemp, G.,Stuart, A.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G. (登録日: 2007-12-04, 公開日: 2008-01-29, 最終更新日: 2024-11-13)

主引用文献

Beswick, P.,Charrier, N.,Clarke, B.,Demont, E.,Dingwall, C.,Dunsdon, R.,Faller, A.,Gleave, R.,Hawkins, J.,Hussain, I.,Johnson, C.N.,Macpherson, D.,Maile, G.,Matico, R.,Milner, P.,Mosley, J.,Naylor, A.,O'Brien, A.,Redshaw, S.,Riddell, D.,Rowland, P.,Skidmore, J.,Soleil, V.,Smith, K.J.,Stanway, S.,Stemp, G.,Stuart, A.,Sweitzer, S.,Theobald, P.,Vesey, D.,Walter, D.S.,Ward, J.,Wayne, G.
Bace-1 Inhibitors Part 3: Identification of Hydroxy Ethylamines (Heas) with Nanomolar Potency in Cells.
Bioorg.Med.Chem.Lett., 18:1022-, 2008

PubMed Abstract: This article is focusing on further optimization of previously described hydroxy ethylamine (HEA) BACE-1 inhibitors obtained from a focused library with the support of X-ray crystallography. Optimization of the non-prime side of our inhibitors and introduction of a 6-membered sultam substituent binding to Asn-294 as well as a fluorine in the C-2 position led to derivatives with nanomolar potency in cell-based assays.

PubMed: 18171615
DOI: 10.1016/J.BMCL.2007.12.020

実験手法

X-RAY DIFFRACTION (1.6 Å)