3l3a: Difference between revisions

← Older edit

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:3l3a.jpg|left|200px]]
-<!--
+==Bace-1 with the aminopyridine Compound 32==
-The line below this paragraph, containing "STRUCTURE_3l3a", creates the "Structure Box" on the page.
+<StructureSection load='3l3a' size='340' side='right'caption='[[3l3a]], [[Resolution|resolution]] 2.36&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'>[[3l3a]] 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=3L3A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L3A 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]] 2.362&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
-{{STRUCTURE_3l3a|  PDB=3l3a  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3l3a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l3a OCA], [https://pdbe.org/3l3a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l3a RCSB], [https://www.ebi.ac.uk/pdbsum/3l3a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l3a 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/l3/3l3a_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=3l3a 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.
-===Bace-1 with the aminopyridine Compound 32===
+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>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 3l3a" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20223661}}, 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 20223661 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20223661}}
+__TOC__
+</StructureSection>
-==About this Structure==
-L3A 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].
-==Reference==
-<ref group="xtra">PMID:20223661</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Chopra, R.]]
+[[Category: Chopra R]]
-[[Category: Olland, A M.]]
+[[Category: Olland AM]]
-[[Category: Aminopyridine]]
-[[Category: Aspartyl protease]]
-[[Category: Bace-1]]
-[[Category: Beta-secretase]]
-[[Category: Disulfide bond]]
-[[Category: Hydrolase]]
-[[Category: Inhibitor]]
-[[Category: Protease]]
-[[Category: Transmembrane]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 28 10:55:11 2010''