2vij
From Proteopedia
(New page: 200px<br /><applet load="2vij" size="350" color="white" frame="true" align="right" spinBox="true" caption="2vij, resolution 1.60Å" /> '''HUMAN BACE-1 IN COMP...) |
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==Overview== | ==Overview== | ||
| - | This article is focusing on further optimization of previously described | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 2VIJ 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=C44:'>C44</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 Sites: <scene name='pdbsite=AC1:C44 Binding Site For Chain A'>AC1</scene> and <scene name='pdbsite=AC2:C44 Binding Site For Chain A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIJ OCA]. | + | 2VIJ 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=C44:'>C44</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 Sites: <scene name='pdbsite=AC1:C44+Binding+Site+For+Chain+A'>AC1</scene> and <scene name='pdbsite=AC2:C44+Binding+Site+For+Chain+A'>AC2</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIJ OCA]. |
==Reference== | ==Reference== | ||
| - | BACE-1 inhibitors part 3: | + | BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, 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 KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18171615 18171615] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Beswick, P.]] | [[Category: Beswick, P.]] | ||
| - | [[Category: Brien, A | + | [[Category: Brien, A O.]] |
[[Category: Charrier, N.]] | [[Category: Charrier, N.]] | ||
[[Category: Clarke, B.]] | [[Category: Clarke, B.]] | ||
| Line 44: | Line 44: | ||
[[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.]] | ||
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[[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 18:56:10 2008'' |
Revision as of 16:56, 21 February 2008
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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
Overview
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.
About this Structure
2VIJ 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 Sites: and . Full crystallographic information is available from OCA.
Reference
BACE-1 inhibitors part 3: identification of hydroxy ethylamines (HEAs) with nanomolar potency in cells., Beswick P, Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Gleave R, Hawkins J, Hussain I, Johnson CN, 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 KJ, Stanway S, Stemp G, Stuart A, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1022-6. Epub 2007 Dec 15. PMID:18171615
Page seeded by OCA on Thu Feb 21 18:56:10 2008
Categories: Homo sapiens | Memapsin 2 | Single protein | Beswick, P. | Brien, A O. | Charrier, N. | Clarke, B. | Demont, E. | Dingwall, C. | Dunsdon, R. | Faller, A. | Gleave, R. | Hawkins, J. | Hussain, I. | Johnson, C. | Macpherson, D. | Maile, G. | Matico, R. | Milner, P. | Mosley, J. | Naylor, A. | Redshaw, S. | Riddell, D. | Rowland, P. | Skidmore, J. | Smith, K. | Soleil, V. | Stanway, S. | Stemp, G. | Stuart, A. | Sweitzer, S. | Theobald, P. | Vesey, D. | Walter, D S. | Ward, J. | Wayne, G. | C44 | Alternative splicing | Asp-2 | Aspartyl protease | Bace-1 | Beta-secretase | Beta-site app cleaving enzyme | Glycoprotein | Hydrolase | Memapsin-2 | Membrane | Protease | Transmembrane | Zymogen
