2wf1
From Proteopedia
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| - | [[ | + | ==HUMAN BACE-1 IN COMPLEX WITH 7-ETHYL-N-((1S,2R)-2-HYDROXY-3-(((3-(METHYLOXY)PHENYL(METHYL)AMINO)-1-(PHENYLMETHYL) PROPYL)-1-METHYL-3,4-DIHYDRO-1H-(1,2,5)THIADIAZEPINO(3,4,5-HI)INDOLE-9-CARBOXAMIDE 2,2-DIOXIDE== |
| + | <StructureSection load='2wf1' size='340' side='right' caption='[[2wf1]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2wf1]] is a 1 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=2WF1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WF1 FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY1:N-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-7-ETHYL-1-METHYL-3,4-DIHYDRO-1H-[1,2,5]THIADIAZEPINO[3,4,5-HI]INDOLE-9-CARBOXAMIDE+2,2-DIOXIDE'>ZY1</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[2vnm|2vnm]], [[1m4h|1m4h]], [[1xn2|1xn2]], [[2fdp|2fdp]], [[2viy|2viy]], [[2vie|2vie]], [[2va6|2va6]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[1sgz|1sgz]], [[2va5|2va5]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vj9|2vj9]], [[2vkm|2vkm]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]], [[2wez|2wez]], [[2wf0|2wf0]], [[2wf2|2wf2]], [[2wf3|2wf3]], [[2wf4|2wf4]]</td></tr> | ||
| + | <tr><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> | ||
| + | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2wf1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wf1 RCSB], [http://www.ebi.ac.uk/pdbsum/2wf1 PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | == Evolutionary Conservation == | ||
| + | [[Image:Consurf_key_small.gif|200px|right]] | ||
| + | Check<jmol> | ||
| + | <jmolCheckbox> | ||
| + | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wf/2wf1_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
| + | <text>to colour the structure by Evolutionary Conservation</text> | ||
| + | </jmolCheckbox> | ||
| + | </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]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Our first generation of hydroxyethylamine transition-state mimetic BACE-1 inhibitors allowed us to validate BACE-1 as a key target for Alzheimer's disease by demonstrating amyloid lowering in an animal model, albeit at rather high doses. Finding a molecule from this series which was active at lower oral doses proved elusive and demonstrated the need to find a novel series of inhibitors with improved pharmacokinetics. This Letter describes the discovery of such inhibitors. | ||
| - | + | Second generation of BACE-1 inhibitors part 2: Optimisation of the non-prime side substituent.,Charrier N, Clarke B, Demont E, Dingwall C, Dunsdon R, Hawkins J, Hubbard J, Hussain I, 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 Bioorg Med Chem Lett. 2009 Jul 1;19(13):3669-73. Epub 2009 Apr 5. PMID:19477642<ref>PMID:19477642</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
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==See Also== | ==See Also== | ||
*[[Beta secretase|Beta secretase]] | *[[Beta secretase|Beta secretase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Memapsin 2]] | [[Category: Memapsin 2]] | ||
Revision as of 08:23, 29 September 2014
HUMAN BACE-1 IN COMPLEX WITH 7-ETHYL-N-((1S,2R)-2-HYDROXY-3-(((3-(METHYLOXY)PHENYL(METHYL)AMINO)-1-(PHENYLMETHYL) 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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Categories: Homo sapiens | Memapsin 2 | Brien, A O. | Charrier, N. | Clarke, B. | Demont, E. | Dingwall, C. | Dunsdon, R. | Hawkins, J. | Hubbard, J. | Hussain, I. | Maile, G. | Matico, R. | Mosley, J. | Naylor, A. | Redshaw, S. | Rowland, P. | Smith, K J. | Soleil, V. | Sweitzer, S. | Theobald, P. | Vesey, D. | Walter, D S. | Wayne, G. | Asp-2 | Aspartyl protease | Bace-1 | Beta-secretase | Beta-site app cleaving enzyme | Disulfide bond | Glycoprotein | Hydrolase | Memapsin-2 | Membrane | Protease | Transmembrane | Zymogen
