4acx: Difference between revisions

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-[[Image:4acx.jpg|left|200px]]
-<!--
+==Aminoimidazoles as BACE-1 Inhibitors. X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 23==
-The line below this paragraph, containing "STRUCTURE_4acx", creates the "Structure Box" on the page.
+<StructureSection load='4acx' size='340' side='right'caption='[[4acx]], [[Resolution|resolution]] 2.00&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'>[[4acx]] 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=4ACX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ACX 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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=S8Z:(8R)-8-[4-(DIFLUOROMETHOXY)PHENYL]-3,3-DIFLUORO-8-[3-(3-METHOXYPROP-1-YN-1-YL)PHENYL]-2,3,4,8-TETRAHYDROIMIDAZO[1,5-A]PYRIMIDIN-6-AMINE'>S8Z</scene></td></tr>
-{{STRUCTURE_4acx|  PDB=4acx  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4acx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4acx OCA], [https://pdbe.org/4acx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4acx RCSB], [https://www.ebi.ac.uk/pdbsum/4acx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4acx 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 ==
+The evaluation of a series of bicyclic aminoimidazoles as potent BACE-1 inhibitors is described. The crystal structures of compounds 14 and 23 in complex with BACE-1 reveal hydrogen bond interactions with the protein important for achieving potent inhibition. The optimization of permeability and efflux properties of the compounds is discussed as well as the importance of these properties for attaining in vivo brain efficacy. Compound (R)-25 was selected for evaluation in vivo in wild type mice and 1.5h after oral co-administration of 300mumol/kg (R)-25 and efflux inhibitor GF120918 the brain Abeta40 level was reduced by 17% and the plasma Abeta40 level by 76%.
-===Aminoimidazoles as BACE-1 Inhibitors. X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 23===
+Aminoimidazoles as BACE-1 inhibitors: The challenge to achieve in vivo brain efficacy.,Swahn BM, Holenz J, Kihlstrom J, Kolmodin K, Lindstrom J, Plobeck N, Rotticci D, Sehgelmeble F, Sundstrom M, Berg S, Falting J, Georgievska B, Gustavsson S, Neelissen J, Ek M, Olsson LL, Berg S Bioorg Med Chem Lett. 2012 Mar 1;22(5):1854-9. Epub 2012 Jan 28. PMID:22325942<ref>PMID:22325942</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 4acx" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_22325942}}, 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 22325942 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_22325942}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[4acx]] is a 1 chain structure with 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=4ACX OCA].
-==Reference==
-<ref group="xtra">PMID:022325942</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Berg, S.]]
+[[Category: Berg S]]
-[[Category: Ek, M.]]
+[[Category: Ek M]]
-[[Category: Falting, J.]]
+[[Category: Falting J]]
-[[Category: Georgievska, B.]]
+[[Category: Georgievska B]]
-[[Category: Gustavsson, S.]]
+[[Category: Gustavsson S]]
-[[Category: Holenz, J.]]
+[[Category: Holenz J]]
-[[Category: Kihlstrom, J.]]
+[[Category: Kihlstrom J]]
-[[Category: Kolmodin, K.]]
+[[Category: Kolmodin K]]
-[[Category: Lindstrom, J.]]
+[[Category: Lindstrom J]]
-[[Category: Neelissen, J.]]
+[[Category: Neelissen J]]
-[[Category: Olsson, L L.]]
+[[Category: Olsson LL]]
-[[Category: Plobeck, N.]]
+[[Category: Plobeck N]]
-[[Category: Rotticci, D.]]
+[[Category: Rotticci D]]
-[[Category: Sehgelmeble, F.]]
+[[Category: Sehgelmeble F]]
-[[Category: Sundstrom, M.]]
+[[Category: Sundstrom M]]
-[[Category: Swahn, B.]]
+[[Category: Swahn B]]
-[[Category: Vonberg, S.]]
+[[Category: Von Berg S]]
-[[Category: Alzheimer's disease]]
-[[Category: Hydrolase]]