2viz
From Proteopedia
(New page: 200px<br /><applet load="2viz" size="350" color="white" frame="true" align="right" spinBox="true" caption="2viz, resolution 1.60Å" /> '''HUMAN BACE-1 IN COMP...) |
|||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Inhibition of the aspartyl protease BACE-1 has the potential to deliver a | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2VIZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=VG4:'>VG4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] Known structural/functional Site: <scene name='pdbsite=AC1:Vg4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIZ OCA]. | + | 2VIZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=VG4:'>VG4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] Known structural/functional Site: <scene name='pdbsite=AC1:Vg4+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIZ OCA]. |
==Reference== | ==Reference== | ||
| - | BACE-1 inhibitors | + | BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs)., 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 KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1011-6. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18171614 18171614] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Brien, A | + | [[Category: Brien, A O.]] |
[[Category: Clarke, B.]] | [[Category: Clarke, B.]] | ||
[[Category: Demont, E.]] | [[Category: Demont, E.]] | ||
| Line 38: | Line 38: | ||
[[Category: Theobald, P.]] | [[Category: Theobald, P.]] | ||
[[Category: Vesey, D.]] | [[Category: Vesey, D.]] | ||
| - | [[Category: Walter, D | + | [[Category: Walter, D S.]] |
[[Category: Ward, J.]] | [[Category: Ward, J.]] | ||
[[Category: Wayne, G.]] | [[Category: Wayne, G.]] | ||
| Line 56: | Line 56: | ||
[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:56:17 2008'' |
Revision as of 16:56, 21 February 2008
|
HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-(2-OXO-1-PYRROLIDINYL)-5-(PROPYLOXY) BENZAMIDE
Overview
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.
About this Structure
2VIZ is a Single protein structure of sequence from Homo sapiens with as ligand. Active as Memapsin 2, with EC number 3.4.23.46 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs)., 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 KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1011-6. Epub 2007 Dec 15. PMID:18171614
Page seeded by OCA on Thu Feb 21 18:56:17 2008
Categories: Homo sapiens | Memapsin 2 | Single protein | Brien, A O. | 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. | Redshaw, S. | Riddell, D. | Rowland, P. | Smith, K. | Soleil, V. | Stanway, S. | Stemp, G. | Sweitzer, S. | Theobald, P. | Vesey, D. | Walter, D S. | Ward, J. | Wayne, G. | VG4 | Alternative splicing | Asp-2 | Aspartyl protease | Bace-1 | Beta-secretase | Beta-site app cleaving enzyme | Glycoprotein | Hydrolase | Memapsin-2 | Membrane | Protease | Transmembrane | Zymogen
