3dv1: Difference between revisions
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New page: '''Unreleased structure''' The entry 3dv1 is ON HOLD until Paper Publication Authors: Rondeau, J.-M. Description: Crystal structure of human beta-secretase in complex with NVP-ARV999 ... |
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==Crystal structure of human beta-secretase in complex with NVP-ARV999== | |||
<StructureSection load='3dv1' size='340' side='right'caption='[[3dv1]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3dv1]] is a 3 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=3DV1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3DV1 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AR9:(2R,4S)-N-BUTYL-4-[(2S,5S,7R)-2,7-DIMETHYL-3,15-DIOXO-1,4-DIAZACYCLOPENTADECAN-5-YL]-4-HYDROXY-2-METHYLBUTANAMIDE'>AR9</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=3dv1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3dv1 OCA], [https://pdbe.org/3dv1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3dv1 RCSB], [https://www.ebi.ac.uk/pdbsum/3dv1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3dv1 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
== 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/dv/3dv1_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=3dv1 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The macrocyclic peptidic BACE-1 inhibitors 2a-c show moderate enzymatic and cellular activity. By exchange of the hydroxyethylene- to ethanolamine-transition state mimetic the peptidic character was reduced, providing the highly potent and selective inhibitor 3. Variation of the P' moiety resulted in the macrocyclic inhibitor 14. Both macrocycles show inhibition of BACE-1 in the brain of APP51/16 transgenic mice, 3 (NB-544) after intravenous and 14 (NB-533) after oral application. | |||
Macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors with activity in vivo.,Machauer R, Laumen K, Veenstra S, Rondeau JM, Tintelnot-Blomley M, Betschart C, Jaton AL, Desrayaud S, Staufenbiel M, Rabe S, Paganetti P, Neumann U Bioorg Med Chem Lett. 2009 Mar 1;19(5):1366-70. Epub 2009 Jan 22. PMID:19195887<ref>PMID:19195887</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3dv1" 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: Rondeau J-M]] | |||
Latest revision as of 05:46, 17 October 2024
Crystal structure of human beta-secretase in complex with NVP-ARV999
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