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2viz

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(New page: 200px<br /><applet load="2viz" size="350" color="white" frame="true" align="right" spinBox="true" caption="2viz, resolution 1.60&Aring;" /> '''HUMAN BACE-1 IN COMP...)
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[[Image:2viz.jpg|left|200px]]<br /><applet load="2viz" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2viz, resolution 1.60&Aring;" />
 
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'''HUMAN BACE-1 IN COMPLEX WITH N-((1S,2R)-3-(((1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL)AMINO)-2-HYDROXY-1-(PHENYLMETHYL)PROPYL)-3-(2-OXO-1-PYRROLIDINYL)-5-(PROPYLOXY) BENZAMIDE'''<br />
 
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==Overview==
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==Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(2-oxo- 1-pyrrolidinyl)-5-(propyloxy)benzamide==
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Inhibition of the aspartyl protease BACE-1 has the potential to deliver a, disease-modifying therapy for Alzheimer's disease. Herein, is described, the lead generation effort which resulted, with the support of X-ray, crystallography, in the discovery of potent inhibitors based on a hydroxy, ethylamine (HEA) transition-state mimetic. These inhibitors were capable, of lowering amyloid production in a cell-based assay.
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<StructureSection load='2viz' size='340' side='right'caption='[[2viz]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2viz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VIZ FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VG4:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(2-OXO-2,3-DIHYDRO-1H-PYRROL-1-YL)-5-PROPOXYBENZAMIDE'>VG4</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2vie|2vie]], [[2va6|2va6]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[1w51|1w51]], [[2viy|2viy]]</div></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2viz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2viz OCA], [https://pdbe.org/2viz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2viz RCSB], [https://www.ebi.ac.uk/pdbsum/2viz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2viz 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/vi/2viz_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/main_output.php?pdb_ID=2viz 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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Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. Herein, is described the lead generation effort which resulted, with the support of X-ray crystallography, in the discovery of potent inhibitors based on a hydroxy ethylamine (HEA) transition-state mimetic. These inhibitors were capable of lowering amyloid production in a cell-based assay.
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==About this Structure==
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BACE-1 inhibitors part 1: identification of novel hydroxy ethylamines (HEAs).,Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G Bioorg Med Chem Lett. 2008 Feb 1;18(3):1011-6. Epub 2007 Dec 15. PMID:18171614<ref>PMID:18171614</ref>
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2VIZ 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=VG4:'>VG4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Known structural/functional Site: <scene name='pdbsite=AC1:Vg4 Binding Site For Chain A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VIZ OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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BACE-1 inhibitors Part 1: Identification of novel hydroxy ethylamines (HEAs)., Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, Macpherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G, Bioorg Med Chem Lett. 2007 Dec 15;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18171614 18171614]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2viz" style="background-color:#fffaf0;"></div>
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[[Category: Memapsin 2]]
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[[Category: Single protein]]
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[[Category: Brien, A.O.]]
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[[Category: Clarke, B.]]
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[[Category: Demont, E.]]
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[[Category: Dingwall, C.]]
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[[Category: Dunsdon, R.]]
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[[Category: Faller, A.]]
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[[Category: Hawkins, J.]]
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[[Category: Hussain, I.]]
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[[Category: Macpherson, D.]]
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[[Category: Maile, G.]]
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[[Category: Matico, R.]]
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[[Category: Milner, P.]]
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[[Category: Mosley, J.]]
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[[Category: Naylor, A.]]
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[[Category: Redshaw, S.]]
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[[Category: Riddell, D.]]
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[[Category: Rowland, P.]]
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[[Category: Smith, K.]]
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[[Category: Soleil, V.]]
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[[Category: Stanway, S.]]
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[[Category: Stemp, G.]]
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[[Category: Sweitzer, S.]]
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[[Category: Theobald, P.]]
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[[Category: Vesey, D.]]
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[[Category: Walter, D.S.]]
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[[Category: Ward, J.]]
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[[Category: Wayne, G.]]
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[[Category: VG4]]
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[[Category: alternative splicing]]
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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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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 11:02:05 2008''
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==See Also==
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
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[[Category: Memapsin 2]]
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[[Category: Brien, A O]]
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[[Category: Clarke, B]]
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[[Category: Demont, E]]
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[[Category: Dingwall, C]]
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[[Category: Dunsdon, R]]
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[[Category: Faller, A]]
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[[Category: Hawkins, J]]
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[[Category: Hussain, I]]
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[[Category: MacPherson, D]]
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[[Category: Maile, G]]
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[[Category: Matico, R]]
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[[Category: Milner, P]]
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[[Category: Mosley, J]]
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[[Category: Naylor, A]]
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[[Category: Redshaw, S]]
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[[Category: Riddell, D]]
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[[Category: Rowland, P]]
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[[Category: Smith, K]]
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[[Category: Soleil, V]]
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[[Category: Stanway, S]]
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[[Category: Stemp, G]]
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[[Category: Sweitzer, S]]
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[[Category: Theobald, P]]
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[[Category: Vesey, D]]
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[[Category: Walter, D S]]
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[[Category: Ward, J]]
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[[Category: Wayne, G]]
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[[Category: Alternative splicing]]
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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]]

Current revision

Human BACE-1 in complex with N-((1S,2R)-3-(((1S)-2-(cyclohexylamino)- 1-methyl-2-oxoethyl)amino)-2-hydroxy-1-(phenylmethyl)propyl)-3-(2-oxo- 1-pyrrolidinyl)-5-(propyloxy)benzamide

PDB ID 2viz

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