2wf4
From Proteopedia
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| - | [[ | + | ==HUMAN BACE-1 IN COMPLEX WITH 6-ETHYL-1-METHYL-N-((1S)-2-OXO-1-(PHENYLMETHYL)-3-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL)-1,3,4,6-TETRAHYDRO(1,2)THIAZEPINO(5,4,3-CD)INDOLE-8-CARBOXAMIDE 2,2-DIOXIDE== |
| + | <StructureSection load='2wf4' size='340' side='right' caption='[[2wf4]], [[Resolution|resolution]] 1.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2wf4]] 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=2WF4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2WF4 FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZY4:N-[(1S)-1-BENZYL-2,2-DIHYDROXY-3-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL]-6-ETHYL-1-METHYL-1,3,4,6-TETRAHYDRO[1,2]THIAZEPINO[5,4,3-CD]INDOLE-8-CARBOXAMIDE+2,2-DIOXIDE'>ZY4</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tqf|1tqf]], [[1xn3|1xn3]], [[1m4h|1m4h]], [[2vnm|2vnm]], [[2fdp|2fdp]], [[1xn2|1xn2]], [[2viy|2viy]], [[2va6|2va6]], [[2vie|2vie]], [[2vj6|2vj6]], [[2viz|2viz]], [[2b8l|2b8l]], [[1ym4|1ym4]], [[2va5|2va5]], [[1sgz|1sgz]], [[1ujk|1ujk]], [[2b8v|2b8v]], [[1fkn|1fkn]], [[1xs7|1xs7]], [[2vij|2vij]], [[2va7|2va7]], [[1ym2|1ym2]], [[2vkm|2vkm]], [[2vj9|2vj9]], [[2vnn|2vnn]], [[1py1|1py1]], [[1w50|1w50]], [[1ujj|1ujj]], [[2vj7|2vj7]], [[1w51|1w51]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2wf0|2wf0]], [[2wez|2wez]], [[2wf2|2wf2]]</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=2wf4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2wf4 RCSB], [http://www.ebi.ac.uk/pdbsum/2wf4 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/2wf4_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 BACE-1 inhibitors proved unlikely to provide molecules that would lower amyloid in an animal model at low oral doses. This observation led us to the discovery of a second generation of inhibitors having nanomolar activity in a cell-based assay and with the potential for improved pharmacokinetic profiles. In this Letter, we describe our successful strategy for the optimization of oral bioavailability and also give insights into the design of compounds with the potential for improved brain penetration. | ||
| - | + | Second generation of BACE-1 inhibitors part 3: Towards non hydroxyethylamine transition state mimetics.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, 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):3674-8. Epub 2009 Apr 5. PMID:19406640<ref>PMID:19406640</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 06:51, 29 September 2014
HUMAN BACE-1 IN COMPLEX WITH 6-ETHYL-1-METHYL-N-((1S)-2-OXO-1-(PHENYLMETHYL)-3-(TETRAHYDRO-2H-PYRAN-4-YLAMINO)PROPYL)-1,3,4,6-TETRAHYDRO(1,2)THIAZEPINO(5,4,3-CD)INDOLE-8-CARBOXAMIDE 2,2-DIOXIDE
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Categories: Homo sapiens | Memapsin 2 | Brien, A O. | Charrier, N. | Clarke, B. | Cutler, L. | Demont, E. | Dingwall, C. | Dunsdon, R. | Hawkins, J. | Howes, C. | 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
