2wez
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 2wez is ON HOLD Authors: Charrier, N., Clarke, B., Cutler, L., Demont, E., Dingwall, C., Dunsdon, R., Hawkins, J., Howes, C., Hubbard, J., Hussain, ...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Human BACE-1 in complex with 1-ethyl-N-((1S,2R)-2-hydroxy-3-(((3-(methyloxy)phenyl)methyl)amino)-1-(phenylmethyl)propyl)-4-(2-oxo-1- pyrrolidinyl)-1H-indole-6-carboxamide== | |
| + | <StructureSection load='2wez' size='340' side='right'caption='[[2wez]], [[Resolution|resolution]] 1.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2wez]] 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=2WEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WEZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZYE:N-{(1S,2R)-1-BENZYL-2-HYDROXY-3-[(3-METHOXYBENZYL)AMINO]PROPYL}-1-ETHYL-4-(2-OXOPYRROLIDIN-1-YL)-1H-INDOLE-6-CARBOXAMIDE'>ZYE</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2wez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wez OCA], [https://pdbe.org/2wez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wez RCSB], [https://www.ebi.ac.uk/pdbsum/2wez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wez ProSAT]</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/we/2wez_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2wez ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. We have recently disclosed a series of transition-state mimetic BACE-1 inhibitors showing nanomolar potency in cell-based assays. Amongst them, GSK188909 (compound 2) had favorable pharmacokinetics and was the first orally bioavailable inhibitor reported to demonstrate brain amyloid lowering in an animal model. In this Letter, we describe the reasons that led us to favor a second generation of inhibitors for further in vivo studies. | ||
| - | + | Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.,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):3664-8. Epub 2009 Apr 17. PMID:19428244<ref>PMID:19428244</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 2wez" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| + | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Charrier N]] | ||
| + | [[Category: Clarke B]] | ||
| + | [[Category: Cutler L]] | ||
| + | [[Category: Demont E]] | ||
| + | [[Category: Dingwall C]] | ||
| + | [[Category: Dunsdon R]] | ||
| + | [[Category: Hawkins J]] | ||
| + | [[Category: Howes C]] | ||
| + | [[Category: Hubbard J]] | ||
| + | [[Category: Hussain I]] | ||
| + | [[Category: Maile G]] | ||
| + | [[Category: Matico R]] | ||
| + | [[Category: Mosley J]] | ||
| + | [[Category: Naylor A]] | ||
| + | [[Category: O'Brien A]] | ||
| + | [[Category: Redshaw S]] | ||
| + | [[Category: Rowland P]] | ||
| + | [[Category: Smith KJ]] | ||
| + | [[Category: Soleil V]] | ||
| + | [[Category: Sweitzer S]] | ||
| + | [[Category: Theobald P]] | ||
| + | [[Category: Vesey D]] | ||
| + | [[Category: Walter DS]] | ||
| + | [[Category: Wayne G]] | ||
Current revision
Human BACE-1 in complex with 1-ethyl-N-((1S,2R)-2-hydroxy-3-(((3-(methyloxy)phenyl)methyl)amino)-1-(phenylmethyl)propyl)-4-(2-oxo-1- pyrrolidinyl)-1H-indole-6-carboxamide
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Categories: Homo sapiens | Large Structures | 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 | Smith KJ | Soleil V | Sweitzer S | Theobald P | Vesey D | Walter DS | Wayne G
