View source for 2ohn

[[Image:2ohn.gif|left|200px]]<br />
<applet load="2ohn" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2ohn, resolution 2.150&Aring;" />
'''X-ray crystal structure of beta secretase complexed with 4-(4-fluorobenzyl)piperidine'''<br />

==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==
2OHN 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 IOD, DMS and 4FP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2OHN 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 Feb 22;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17315856 17315856]
[[Category: Homo sapiens]]
[[Category: Memapsin 2]]
[[Category: Single protein]]
[[Category: Patel, S.]]
[[Category: 4FP]]
[[Category: DMS]]
[[Category: IOD]]
[[Category: alternative splicing]]
[[Category: alzheimer's disease]]
[[Category: aspartic protease]]
[[Category: aspartyl protease]]
[[Category: base]]
[[Category: beta-secretase]]
[[Category: glycoprotein]]
[[Category: hydrolase]]
[[Category: memapsin 2]]
[[Category: signal]]
[[Category: transmembrane]]
[[Category: zymogen]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:11:00 2007''