2ohu

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{{Seed}}
 
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[[Image:2ohu.png|left|200px]]
 
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==X-ray crystal structure of beta secretase complexed with compound 8b==
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The line below this paragraph, containing "STRUCTURE_2ohu", creates the "Structure Box" on the page.
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<StructureSection load='2ohu' size='340' side='right'caption='[[2ohu]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2ohu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2OHU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2OHU FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=IP7:N~3~-[5-(1H-INDOL-6-YL)-2-(PYRIDIN-2-YLMETHOXY)BENZYL]PYRIDINE-2,3-DIAMINE'>IP7</scene></td></tr>
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{{STRUCTURE_2ohu| PDB=2ohu | SCENE= }}
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ohu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohu OCA], [https://pdbe.org/2ohu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ohu RCSB], [https://www.ebi.ac.uk/pdbsum/2ohu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ohu ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref>
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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/oh/2ohu_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2ohu 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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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).
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===X-ray crystal structure of beta secretase complexed with compound 8b===
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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:17315857<ref>PMID:17315857</ref>
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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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<div class="pdbe-citations 2ohu" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_17315857}}, adds the Publication Abstract to the page
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 17315857 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_17315857}}
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__TOC__
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</StructureSection>
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==About this Structure==
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2OHU 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=2OHU OCA].
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==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://www.ncbi.nlm.nih.gov/pubmed/17315857 17315857]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Patel S]]
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[[Category: Patel, S.]]
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[[Category: Alternative splicing]]
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[[Category: Alzheimer's disease]]
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[[Category: Aspartic protease]]
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[[Category: Aspartyl protease]]
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[[Category: Base]]
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[[Category: Beta-secretase]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Memapsin 2]]
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[[Category: Signal]]
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[[Category: Transmembrane]]
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[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:13:04 2008''
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Current revision

X-ray crystal structure of beta secretase complexed with compound 8b

PDB ID 2ohu

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