2ohq: Difference between revisions
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[[Image:2ohq.gif|left|200px]] | [[Image:2ohq.gif|left|200px]] | ||
'''X-ray crystal structure of beta secretase complexed with compound 4''' | {{Structure | ||
|PDB= 2ohq |SIZE=350|CAPTION= <scene name='initialview01'>2ohq</scene>, resolution 2.100Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=7IP:6-[2-(3'-METHOXYBIPHENYL-3-YL)ETHYL]PYRIDIN-2-AMINE'>7IP</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [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] | |||
|GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | |||
}} | |||
'''X-ray crystal structure of beta secretase complexed with compound 4''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2OHQ is a [ | 2OHQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OHQ OCA]. | ||
==Reference== | ==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:[http:// | 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://www.ncbi.nlm.nih.gov/pubmed/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 Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:59:55 2008'' | ||
Revision as of 18:59, 20 March 2008
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| , resolution 2.100Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , and | ||||||
| Gene: | BACE1, BACE (Homo sapiens) | ||||||
| Activity: | Memapsin 2, with EC number 3.4.23.46 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
X-ray crystal structure of beta secretase complexed with compound 4
OverviewOverview
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 StructureAbout this Structure
2OHQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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
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