3ixk

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[[Image:3ixk.png|left|200px]]
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==Potent beta-secretase 1 inhibitor==
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<StructureSection load='3ixk' size='340' side='right' caption='[[3ixk]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3ixk]] is a 3 chain structure with 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=3IXK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3IXK FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=929:N-[(2S,3S,5R)-1-[(3,5-DIFLUOROPHENYL)METHOXY]-3-HYDROXY-5-METHYL-6-[[(2S)-3-METHYL-1-OXO-1-(PHENYLMETHYLAMINO)BUTAN-2-YL]AMINO]-6-OXO-HEXAN-2-YL]-5-(METHYL-METHYLSULFONYL-AMINO)-N-[(1R)-1-PHENYLETHYL]BENZENE-1,3-DICARBOXAMIDE'>929</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ixk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ixk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ixk RCSB], [http://www.ebi.ac.uk/pdbsum/3ixk PDBsum]</span></td></tr>
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</table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ix/3ixk_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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We herein describe the design and synthesis of a series of BACE-1 inhibitors incorporating a P1-substituted hydroxylethylene transition state isostere. The synthetic route starting from commercially available carbohydrates yielded a pivotal lactone intermediate with excellent stereochemical control which subsequently could be diversified at the P1-position. The final inhibitors were optimized using three different amines to provide the residues in the P2'-P3' position and three different acids affording the residues in the P2-P3 position. In addition we report on the stereochemical preference of the P1'-methyl substituent in the synthesized inhibitors. All inhibitors were evaluated in an in vitro BACE-1 assay where the most potent inhibitor, 34-(R), exhibited a BACE-1 IC(50) value of 3.1 nM.
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{{STRUCTURE_3ixk| PDB=3ixk | SCENE= }}
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Synthesis of potent BACE-1 inhibitors incorporating a hydroxyethylene isostere as central core.,Wangsell F, Gustafsson K, Kvarnstrom I, Borkakoti N, Edlund M, Jansson K, Lindberg J, Hallberg A, Rosenquist A, Samuelsson B Eur J Med Chem. 2010 Mar;45(3):870-82. Epub 2009 Nov 12. PMID:20036448<ref>PMID:20036448</ref>
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===Potent beta-secretase 1 inhibitor===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_20036448}}
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==About this Structure==
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[[3ixk]] is a 3 chain structure with 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=3IXK OCA].
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==See Also==
==See Also==
*[[Beta secretase|Beta secretase]]
*[[Beta secretase|Beta secretase]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020036448</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Memapsin 2]]
[[Category: Memapsin 2]]
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[[Category: Borkakoti, N.]]
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[[Category: Borkakoti, N]]
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[[Category: Lindberg, J D.]]
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[[Category: Lindberg, J D]]
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[[Category: Nystrom, S.]]
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[[Category: Nystrom, S]]
[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
[[Category: Bace]]
[[Category: Bace]]

Revision as of 09:26, 8 December 2014

Potent beta-secretase 1 inhibitor

3ixk, resolution 2.50Å

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