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2wf0

From Proteopedia

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{{Seed}}
 
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[[Image:2wf0.jpg|left|200px]]
 
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==Human BACE-1 in complex with 4-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-8-(2-oxo-1-pyrrolidinyl)-6-quinolinecarboxamide==
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The line below this paragraph, containing "STRUCTURE_2wf0", creates the "Structure Box" on the page.
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<StructureSection load='2wf0' size='340' side='right'caption='[[2wf0]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2wf0]] 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=2WF0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WF0 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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=ZY0:N-[(1S,2R)-1-BENZYL-2-HYDROXY-3-{[3-(TRIFLUOROMETHYL)BENZYL]AMINO}PROPYL]-4-ETHYL-8-(2-OXOPYRROLIDIN-1-YL)QUINOLINE-6-CARBOXAMIDE'>ZY0</scene></td></tr>
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-->
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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]], [[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]], [[2wf3|2wf3]], [[2wf1|2wf1]], [[2wf4|2wf4]], [[2wez|2wez]], [[2wf2|2wf2]]</div></td></tr>
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{{STRUCTURE_2wf0| PDB=2wf0 | SCENE= }}
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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=2wf0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wf0 OCA], [https://pdbe.org/2wf0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wf0 RCSB], [https://www.ebi.ac.uk/pdbsum/2wf0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wf0 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/wf/2wf0_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=2wf0 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. 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.
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===HUMAN BACE-1 IN COMPLEX WITH 4-ETHYL-N-((1S,2R)-2-HYDROXY-1-(PHENYLMETHYL)-3-(((3-(TRIFLUOROMETHYL)PHENYL)METHYL)AMINO) PROPYL)-8-(2-OXO-1-PYRROLIDINYL)-6-QUINOLINECARBOXAMIDE===
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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>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2wf0" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19428244}}, adds the Publication Abstract to the page
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*[[Beta secretase 3D structures|Beta secretase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19428244 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19428244}}
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__TOC__
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</StructureSection>
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==About this Structure==
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[[Category: Human]]
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2WF0 is a 1 chain structure of 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=2WF0 OCA].
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[[Category: Large Structures]]
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==Reference==
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<ref group="xtra">PMID:19428244</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
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[[Category: Memapsin 2]]
[[Category: Memapsin 2]]
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[[Category: Brien, A O.]]
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[[Category: Brien, A O]]
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[[Category: Charrier, N.]]
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[[Category: Charrier, N]]
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[[Category: Clarke, B.]]
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[[Category: Clarke, B]]
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[[Category: Cutler, L.]]
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[[Category: Cutler, L]]
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[[Category: Demont, E.]]
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[[Category: Demont, E]]
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[[Category: Dingwall, C.]]
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[[Category: Dingwall, C]]
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[[Category: Dunsdon, R.]]
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[[Category: Dunsdon, R]]
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[[Category: Hawkins, J.]]
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[[Category: Hawkins, J]]
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[[Category: Howes, C.]]
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[[Category: Howes, C]]
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[[Category: Hubbard, J.]]
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[[Category: Hubbard, J]]
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[[Category: Hussain, I.]]
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[[Category: Hussain, I]]
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[[Category: Maile, G.]]
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[[Category: Maile, G]]
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[[Category: Matico, R.]]
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[[Category: Matico, R]]
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[[Category: Mosley, J.]]
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[[Category: Mosley, J]]
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[[Category: Naylor, A.]]
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[[Category: Naylor, A]]
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[[Category: Redshaw, S.]]
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[[Category: Redshaw, S]]
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[[Category: Rowland, P.]]
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[[Category: Rowland, P]]
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[[Category: Smith, K J.]]
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[[Category: Smith, K J]]
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[[Category: Soleil, V.]]
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[[Category: Soleil, V]]
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[[Category: Sweitzer, S.]]
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[[Category: Sweitzer, S]]
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[[Category: Theobald, P.]]
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[[Category: Theobald, P]]
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[[Category: Vesey, D.]]
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[[Category: Vesey, D]]
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[[Category: Walter, D S.]]
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[[Category: Walter, D S]]
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[[Category: Wayne, G.]]
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[[Category: Wayne, G]]
[[Category: Alternative splicing]]
[[Category: Alternative splicing]]
[[Category: Asp-2]]
[[Category: Asp-2]]
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[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zymogen]]
[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed May 20 17:20:01 2009''
 

Current revision

Human BACE-1 in complex with 4-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-8-(2-oxo-1-pyrrolidinyl)-6-quinolinecarboxamide

PDB ID 2wf0

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