2ohl

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[[Image:2ohl.gif|left|200px]]<br /><applet load="2ohl" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:2ohl.gif|left|200px]]
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caption="2ohl, resolution 2.650&Aring;" />
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'''X-ray crystal structure of beta secretase complexed with 2-aminoquinoline'''<br />
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{{Structure
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|PDB= 2ohl |SIZE=350|CAPTION= <scene name='initialview01'>2ohl</scene>, resolution 2.650&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=2AQ:QUINOLIN-2-AMINE'>2AQ</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 2-aminoquinoline'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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2OHL 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=2AQ:'>2AQ</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=2OHL OCA].
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2OHL 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=2OHL OCA].
==Reference==
==Reference==
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Application of fragment screening by X-ray crystallography to beta-secretase., Murray CW, Callaghan O, Chessari G, Cleasby A, Congreve M, Frederickson M, Hartshorn MJ, McMenamin R, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1116-23. Epub 2007 Feb 22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17315856 17315856]
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Application of fragment screening by X-ray crystallography to beta-secretase., Murray CW, Callaghan O, Chessari G, Cleasby A, Congreve M, Frederickson M, Hartshorn MJ, McMenamin R, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1116-23. Epub 2007 Feb 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17315856 17315856]
[[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 18:18:35 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:59:50 2008''

Revision as of 15:59, 20 March 2008

Image:2ohl.gif


PDB ID 2ohl

Drag the structure with the mouse to rotate
, resolution 2.650Å
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 2-aminoquinoline


Overview

This paper describes an application of fragment screening to the aspartyl protease enzyme, beta-secretase (BACE-1), using high throughput X-ray crystallography. Three distinct chemotypes were identified by X-ray crystallography as binding to the catalytic aspartates either via an aminoheterocycle (such as 2-aminoquinoline), a piperidine, or an aliphatic hydroxyl group. The fragment hits were weak inhibitors of BACE-1 in the millimolar range but were of interest because most of them displayed relatively good ligand efficiencies. The aminoheterocycles exhibited a novel recognition motif that has not been seen before with aspartic proteases. Virtual screening around this motif identified an aminopyridine with increased potency and attractive growth points for further elaboration using structure-based drug design. The companion paper illustrates how sub-micromolar inhibitors were developed starting from this fragment.

About this Structure

2OHL 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 beta-secretase., Murray CW, Callaghan O, Chessari G, Cleasby A, Congreve M, Frederickson M, Hartshorn MJ, McMenamin R, Patel S, Wallis N, J Med Chem. 2007 Mar 22;50(6):1116-23. Epub 2007 Feb 22. PMID:17315856

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