2vj6

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[[Image:2vj6.jpg|left|200px]]<br /><applet load="2vj6" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="2vj6, resolution 1.80&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-(ETHYLAMINO)-5-(2-OXO-1-PYRROLIDINYL)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-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide==
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<StructureSection load='2vj6' size='340' side='right'caption='[[2vj6]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2vj6]] 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=2VJ6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VJ6 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=VG5:N-[(1S,2R)-1-BENZYL-3-{[(1S)-2-(CYCLOHEXYLAMINO)-1-METHYL-2-OXOETHYL]AMINO}-2-HYDROXYPROPYL]-3-(ETHYLAMINO)-5-(2-OXOPYRROLIDIN-1-YL)BENZAMIDE'>VG5</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]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[2b8v|2b8v]], [[1ujk|1ujk]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[1w51|1w51]], [[2vj7|2vj7]]</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=2vj6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vj6 OCA], [https://pdbe.org/2vj6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vj6 RCSB], [https://www.ebi.ac.uk/pdbsum/2vj6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vj6 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/vj/2vj6_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=2vj6 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 ==
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.
This paper describes the discovery of non-peptidic, potent, and selective hydroxy ethylamine (HEA) inhibitors of BACE-1 by replacement of the prime side of a lead di-amide 2. Inhibitors with nanosmolar potency and high selectivity were identified. Depending on the nature of the P(1)(') and P(2)(') substituents, two different binding modes were observed in X-ray co-crystal structures.
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==About this Structure==
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BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character.,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):1017-21. Epub 2007 Dec 15. PMID:18166458<ref>PMID:18166458</ref>
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2VJ6 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=VG5:'>VG5</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:Vg5+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VJ6 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 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character., 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):1017-21. Epub 2007 Dec 15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18166458 18166458]
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</div>
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[[Category: Homo sapiens]]
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<div class="pdbe-citations 2vj6" 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: VG5]]
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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 Feb 21 18:56:22 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: Glycoprotein]]
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[[Category: Hydrolase]]
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[[Category: Memapsin-2]]
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[[Category: Membrane]]

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-(ethylamino)-5-(2-oxo-1-pyrrolidinyl)benzamide

PDB ID 2vj6

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