4ivt: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 4ivt is ON HOLD
+==Crystal structure of BACE1 with its inhibitor==
+<StructureSection load='4ivt' size='340' side='right'caption='[[4ivt]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4ivt]] 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=4IVT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IVT 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]] 1.6&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=VTI:N-{N-[4-(ACETYLAMINO)-3,5-DICHLOROBENZYL]CARBAMIMIDOYL}-2-(1H-INDOL-1-YL)ACETAMIDE'>VTI</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=4ivt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ivt OCA], [https://pdbe.org/4ivt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ivt RCSB], [https://www.ebi.ac.uk/pdbsum/4ivt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ivt 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>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Proteolytic cleavage of amyloid precursor protein by beta-secretase (BACE1) is a key step in generating the N-terminal of beta-amyloid (Abeta), which further forms into amyloid plaques that are considered as the hallmark of Alzheimer's disease. Inhibitors of BACE1 can reduce the levels of Abeta and thus have a therapeutic potential for treating the disease. We report here the identification of a series of small molecules bearing an indole acylguanidine core structure as potent BACE1 inhibitors. The initial weak fragment was discovered by virtual screening, and followed with a hit-to-lead optimization. With the aid of co-crystal structures of two discovered inhibitors (compounds 19 and 25) with BACE1, we explored the SAR around the indole and aryl groups, and obtained several BACE1 inhibitors about 1,000-fold more potent than the initial fragment hit. Accompanying the lead optimization, a previously under-explored sub-site opposite the flap loop was redefined as a potential binding site for later BACE1 inhibitor design.
-Authors: Chen,T.T., Li,L., Chen,W.Y., Xu,Y.C.
+Virtual screening and structure-based discovery of indole acylguanidines as potent beta-secretase (BACE1) inhibitors.,Zou Y, Li L, Chen W, Chen T, Ma L, Wang X, Xiong B, Xu Y, Shen J Molecules. 2013 May 16;18(5):5706-22. doi: 10.3390/molecules18055706. PMID:23681056<ref>PMID:23681056</ref>
-Description: CRYSTAL STRUCTURE OF BACE1 WITH ITS INHIBITOR
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4ivt" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+*[[Beta-secretase 1|Beta-secretase 1]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Chen TT]]
+[[Category: Chen WY]]
+[[Category: Li L]]
+[[Category: Xu YC]]