2ze1: Difference between revisions

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-{{Seed}}
-[[Image:2ze1.jpg|left|200px]]
-<!--
+==X-ray structure of Bace-1 in complex with compound 6g==
-The line below this paragraph, containing "STRUCTURE_2ze1", creates the "Structure Box" on the page.
+<StructureSection load='2ze1' size='340' side='right'caption='[[2ze1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2ze1]] 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=2ZE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZE1 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.2&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=411:3-BROMO-N-[4-[1-(2-CARBAMIMIDAMIDO-2-OXO-ETHYL)-5-PHENYL-PYRROL-2-YL]PHENYL]BENZAMIDE'>411</scene></td></tr>
-{{STRUCTURE_2ze1|  PDB=2ze1  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ze1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ze1 OCA], [https://pdbe.org/2ze1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ze1 RCSB], [https://www.ebi.ac.uk/pdbsum/2ze1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ze1 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/ze/2ze1_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=2ze1 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Proteolytic cleavage of amyloid precursor protein by beta-secretase (BACE-1) and gamma-secretase leads to formation of beta-amyloid (A beta) a key component of amyloid plaques, which are considered the hallmark of Alzheimer's disease. Small molecule inhibitors of BACE-1 may reduce levels of A beta and thus have therapeutic potential for treating Alzheimer's disease. We recently reported the identification of a novel small molecule BACE-1 inhibitor N-[2-(2,5-diphenyl-pyrrol-1-yl)-acetyl]guanidine (3.a.1). We report here the initial hit-to-lead optimization of this hit and the SAR around the aryl groups occupying the S(1) and S(2') pockets leading to submicromolar BACE-1 inhibitors.
-===X-ray structure of Bace-1 in complex with compound 6g===
+Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets.,Cole DC, Stock JR, Chopra R, Cowling R, Ellingboe JW, Fan KY, Harrison BL, Hu Y, Jacobsen S, Jennings LD, Jin G, Lohse PA, Malamas MS, Manas ES, Moore WJ, O'Donnell MM, Olland AM, Robichaud AJ, Svenson K, Wu J, Wagner E, Bard J Bioorg Med Chem Lett. 2008 Feb 1;18(3):1063-6. Epub 2007 Dec 10. PMID:18162398<ref>PMID:18162398</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2ze1" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_18162398}}, adds the Publication Abstract to the page
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 18162398 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_18162398}}
+__TOC__
+</StructureSection>
-==About this Structure==
-ZE1 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=2ZE1 OCA].
-==Reference==
-Acylguanidine inhibitors of beta-secretase: optimization of the pyrrole ring substituents extending into the S1 and S3 substrate binding pockets., Cole DC, Stock JR, Chopra R, Cowling R, Ellingboe JW, Fan KY, Harrison BL, Hu Y, Jacobsen S, Jennings LD, Jin G, Lohse PA, Malamas MS, Manas ES, Moore WJ, O'Donnell MM, Olland AM, Robichaud AJ, Svenson K, Wu J, Wagner E, Bard J, Bioorg Med Chem Lett. 2008 Feb 1;18(3):1063-6. Epub 2007 Dec 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18162398 18162398]
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Chopra, R.]]
+[[Category: Chopra R]]
-[[Category: Olland, A.]]
+[[Category: Olland A]]
-[[Category: Acylguanidine inhibitor]]
-[[Category: Alternative splicing]]
-[[Category: Aspartyl protease]]
-[[Category: Bace]]
-[[Category: Glycoprotein]]
-[[Category: Hydrolase]]
-[[Category: Membrane]]
-[[Category: Transmembrane]]
-[[Category: Zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 10 14:57:36 2008''