2vnn

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[[Image:2vnn.png|left|200px]]
 
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{{STRUCTURE_2vnn| PDB=2vnn | SCENE= }}
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==Human BACE-1 in complex with 7-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-1- methyl-3,4-dihydro-1H-(1,2,5)thiadiazepino(3,4,5-hi)indole-9- carboxamide 2,2-dioxide==
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<StructureSection load='2vnn' size='340' side='right'caption='[[2vnn]], [[Resolution|resolution]] 1.87&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2vnn]] 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=2VNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VNN FirstGlance]. <br>
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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]] 1.87&#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=CM7:N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)BENZYL]AMINO}PROPYL]-7-ETHYL-1-METHYL-3,4-DIHYDRO-1H-[1,2,5]THIADIAZEPINO[3,4,5-HI]INDOLE-9-CARBOXAMIDE+2,2-DIOXIDE'>CM7</scene></td></tr>
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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=2vnn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vnn OCA], [https://pdbe.org/2vnn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vnn RCSB], [https://www.ebi.ac.uk/pdbsum/2vnn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vnn 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/vn/2vnn_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=2vnn 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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BACE-1 inhibition has the potential to provide a disease-modifying therapy for the treatment of Alzheimer's disease. Optimization of a first generation of BACE-1 inhibitors led to the discovery of novel hydroxyethylamines (HEAs) bearing a tricyclic nonprime side. These derivatives have nanomolar cell potency and are orally bioavailable.
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===HUMAN BACE-1 IN COMPLEX WITH 7-ETHYL-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL)-1-METHYL-3,4-DIHYDRO-1H-(1,2,5)THIADIAZEPINO(3,4,5-HI)INDOLE-9-CARBOXAMIDE 2,2-DIOXIDE===
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Second Generation of Hydroxyethylamine BACE-1 Inhibitors: Optimizing Potency and Oral Bioavailability.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, East P, Hawkins J, Howes C, Hussain I, Jeffrey P, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G J Med Chem. 2008 May 6;. PMID:18457381<ref>PMID:18457381</ref>
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{{ABSTRACT_PUBMED_18457381}}
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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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==About this Structure==
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<div class="pdbe-citations 2vnn" style="background-color:#fffaf0;"></div>
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[[2vnn]] is a 1 chain structure of [[Beta secretase]] 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=2VNN OCA].
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==See Also==
==See Also==
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*[[Beta secretase|Beta secretase]]
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:018457381</ref><references group="xtra"/>
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__TOC__
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</StructureSection>
[[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: Charrier, N.]]
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[[Category: Charrier N]]
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[[Category: Clarke, B.]]
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[[Category: Clarke B]]
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[[Category: Cutler, L.]]
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[[Category: Cutler L]]
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[[Category: Demont, E.]]
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[[Category: Demont E]]
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[[Category: Dingwall, C.]]
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[[Category: Dingwall C]]
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[[Category: Dunsdon, R.]]
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[[Category: Dunsdon R]]
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[[Category: East, P.]]
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[[Category: East P]]
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[[Category: Hawkins, J.]]
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[[Category: Hawkins J]]
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[[Category: Howes, C.]]
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[[Category: Howes C]]
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[[Category: Hussain, I.]]
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[[Category: Hussain I]]
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[[Category: Jeffrey, P.]]
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[[Category: Jeffrey P]]
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[[Category: Maile, G.]]
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[[Category: Maile G]]
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[[Category: Matico, R.]]
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[[Category: Matico R]]
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[[Category: Mosley, J.]]
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[[Category: Mosley J]]
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[[Category: Naylor, A.]]
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[[Category: Naylor A]]
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[[Category: Obrien, A.]]
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[[Category: OBrien A]]
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[[Category: Redshaw, S.]]
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[[Category: Redshaw S]]
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[[Category: Rowland, P.]]
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[[Category: Rowland P]]
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[[Category: Smith, K J.]]
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[[Category: Smith KJ]]
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[[Category: Soleil, V.]]
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[[Category: Soleil V]]
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[[Category: Sweitzer, S.]]
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[[Category: Sweitzer S]]
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[[Category: Theobald, P.]]
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[[Category: Theobald P]]
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[[Category: Vesey, D.]]
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[[Category: Vesey D]]
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[[Category: Walter, D S.]]
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[[Category: Walter DS]]
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[[Category: Wayne, G.]]
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[[Category: Wayne G]]
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[[Category: Asp-2]]
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[[Category: Aspartyl protease]]
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[[Category: Bace-1]]
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[[Category: Beta-secretase]]
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[[Category: Beta-site app cleaving enzyme]]
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[[Category: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Memapsin-2]]
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[[Category: Membrane]]
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[[Category: Protease]]
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[[Category: Transmembrane]]
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[[Category: Zymogen]]
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Current revision

Human BACE-1 in complex with 7-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-1- methyl-3,4-dihydro-1H-(1,2,5)thiadiazepino(3,4,5-hi)indole-9- carboxamide 2,2-dioxide

PDB ID 2vnn

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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