3l3a: Difference between revisions

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-[[Image:3l3a.png|left|200px]]
+==Bace-1 with the aminopyridine Compound 32==
+<StructureSection load='3l3a' size='340' side='right' caption='[[3l3a]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3l3a]] 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=3L3A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L3A FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=625:4-(4-{1-[(6-AMINOPYRIDIN-2-YL)METHYL]-5-(2-CHLOROPHENYL)-1H-PYRROL-2-YL}PHENOXY)BUTANENITRILE'>625</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l38|3l38]]</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE, KIAA1149 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3l3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l3a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3l3a RCSB], [http://www.ebi.ac.uk/pdbsum/3l3a PDBsum]</span></td></tr>
+</table>
+== 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/l3/3l3a_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid in Alzheimer's disease. Recently, we reported small molecule acylguanidines as potent BACE1 inhibitors. However, many of these acylguanidines have a high polar surface area (e.g. as measured by the topological polar surface area or TPSA), which is unfavorable for crossing the blood-brain barrier. Herein, we describe the identification of the 2-aminopyridine moiety as a bioisosteric replacement of the acylguanidine moiety, which resulted in inhibitors with lower TPSA values and superior brain penetration. X-ray crystallographic studies indicated that the 2-aminopyridine moiety interacts directly with the catalytic aspartic acids Asp32 and Asp228 via a hydrogen-bonding network.
-{{STRUCTURE_3l3a|  PDB=3l3a  |  SCENE=  }}
+Novel pyrrolyl 2-aminopyridines as potent and selective human beta-secretase (BACE1) inhibitors.,Malamas MS, Barnes K, Hui Y, Johnson M, Lovering F, Condon J, Fobare W, Solvibile W, Turner J, Hu Y, Manas ES, Fan K, Olland A, Chopra R, Bard J, Pangalos MN, Reinhart P, Robichaud AJ Bioorg Med Chem Lett. 2010 Apr 1;20(7):2068-73. Epub 2010 Feb 23. PMID:20223661<ref>PMID:20223661</ref>
-===Bace-1 with the aminopyridine Compound 32===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_20223661}}
-==About this Structure==
-[[3l3a]] 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=3L3A OCA].
 ==See Also==
 *[[Beta secretase|Beta secretase]]
+== References ==
-==Reference==
+<references/>
-<ref group="xtra">PMID:020223661</ref><references group="xtra"/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
 [[Category: Memapsin 2]]
-[[Category: Chopra, R.]]
+[[Category: Chopra, R]]
-[[Category: Olland, A M.]]
+[[Category: Olland, A M]]
 [[Category: Aminopyridine]]
 [[Category: Aspartyl protease]]