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==Crystal structure of BACE-1 in complex with inhibitor== | |||
<StructureSection load='3ckp' size='340' side='right'caption='[[3ckp]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ckp]] 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=3CKP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKP 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=012:(4S)-N-[(1S,2R)-1-BENZYL-3-{[3-(DIMETHYLAMINO)BENZYL]AMINO}-2-HYDROXYPROPYL]-1-(3-METHOXYBENZYL)-2-OXOIMIDAZOLIDINE-4-CARBOXAMIDE'>012</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=3ckp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ckp OCA], [https://pdbe.org/3ckp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ckp RCSB], [https://www.ebi.ac.uk/pdbsum/3ckp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ckp 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/ck/3ckp_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=3ckp ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3. | |||
Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.,Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152<ref>PMID:18434152</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ckp" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Beta secretase|Beta secretase]] | *[[Beta secretase 3D structures|Beta secretase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Min | [[Category: Min K]] | ||
Latest revision as of 08:44, 17 October 2024
Crystal structure of BACE-1 in complex with inhibitorCrystal structure of BACE-1 in complex with inhibitor
Structural highlights
FunctionBACE1_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.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedWe describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3. Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.,Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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