2oht

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[[Image:2oht.gif|left|200px]]<br /><applet load="2oht" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2oht.gif|left|200px]]
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caption="2oht, resolution 2.30&Aring;" />
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'''X-ray crystal structure of beta secretase complexed with compound 7'''<br />
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{{Structure
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|PDB= 2oht |SIZE=350|CAPTION= <scene name='initialview01'>2oht</scene>, resolution 2.30&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene> and <scene name='pdbligand=IP6:N~3~-[3-(1H-INDOL-6-YL)BENZYL]PYRIDINE-2,3-DIAMINE'>IP6</scene>
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|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]
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|GENE= BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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}}
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'''X-ray crystal structure of beta secretase complexed with compound 7'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2OHT 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=IOD:'>IOD</scene>, <scene name='pdbligand=DMS:'>DMS</scene> and <scene name='pdbligand=IP6:'>IP6</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OHT OCA].
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2OHT 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=2OHT OCA].
==Reference==
==Reference==
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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]
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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]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:18:44 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:59:55 2008''

Revision as of 15:59, 20 March 2008

Image:2oht.gif


PDB ID 2oht

Drag the structure with the mouse to rotate
, resolution 2.30Å
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 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. 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

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