2ohq: Difference between revisions
New page: left|200px<br /> <applet load="2ohq" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ohq, resolution 2.100Å" /> '''X-ray crystal stru... |
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[[Image:2ohq.gif|left|200px]]<br /> | [[Image:2ohq.gif|left|200px]]<br /><applet load="2ohq" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2ohq, resolution 2.100Å" /> | caption="2ohq, resolution 2.100Å" /> | ||
'''X-ray crystal structure of beta secretase complexed with compound 4'''<br /> | '''X-ray crystal structure of beta secretase complexed with compound 4'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
2OHQ 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, 7IP and GOL 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:// | 2OHQ 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>, <scene name='pdbligand=7IP:'>7IP</scene> and <scene name='pdbligand=GOL:'>GOL</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=2OHQ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: zymogen]] | [[Category: zymogen]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 15:25:25 2008'' | ||
Revision as of 16:25, 23 January 2008
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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 muM) and 6c, (IC50 = 24 muM) 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 with , , and as ligands. Active as Memapsin 2, with EC number 3.4.23.46 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 Feb 22;. PMID:17315857
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