2oht
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Fragment-based lead discovery has been successfully applied to the | + | Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM). |
==About this Structure== | ==About this Structure== | ||
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==Reference== | ==Reference== | ||
| - | Application of | + | Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase., Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17315857 17315857] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:18:44 2008'' |
Revision as of 16:18, 21 February 2008
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X-ray crystal structure of beta secretase complexed with compound 7
Overview
Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).
About this Structure
2OHT is a Single protein structure of sequence from Homo sapiens with , and as ligands. Active as Memapsin 2, with EC number 3.4.23.46 Full crystallographic information is available from OCA.
Reference
Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase., Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:17315857
Page seeded by OCA on Thu Feb 21 18:18:44 2008
Categories: Homo sapiens | Memapsin 2 | Single protein | Patel, S. | DMS | IOD | IP6 | Alternative splicing | Alzheimer's disease | Aspartic protease | Aspartyl protease | Base | Beta-secretase | Glycoprotein | Hydrolase | Signal | Transmembrane | Zymogen
