1ym4: Difference between revisions

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-{{Seed}}
-[[Image:1ym4.png|left|200px]]
-<!--
+==Crystal structure of human beta secretase complexed with NVP-AMK640==
-The line below this paragraph, containing "STRUCTURE_1ym4", creates the "Structure Box" on the page.
+<StructureSection load='1ym4' size='340' side='right'caption='[[1ym4]], [[Resolution|resolution]] 2.25&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'>[[1ym4]] is a 6 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=1YM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YM4 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]] 2.25&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=24M:(1R,2R)-2-[(1S,2S)-2-AMINO-1-HYDROXY-4-METHYLPENTYL]CYCLOPENTANECARBOXYLIC+ACID'>24M</scene></td></tr>
-{{STRUCTURE_1ym4|  PDB=1ym4  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ym4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ym4 OCA], [https://pdbe.org/1ym4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ym4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ym4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ym4 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/ym/1ym4_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=1ym4 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Molecular modeling based on the X-ray crystal structure of the Tang-Ghosh heptapeptide inhibitor 1 (OM99-2) of BACE led to the design and synthesis of a series of constrained P(1)' analogues. A cyclopentane ring was incorporated in 1 spanning the P(1)' Ala methyl group and the adjacent methylene carbon atom of the chain. Progressive truncation at the P(2)'-P(4)' sites led to a potent truncated analogue 5 with good selectivity over Cathepsin D. Using the same backbone replacement concept, a series of cyclopentane, cyclopentanone, tetrahydrofuran, pyrrolidine, and pyrrolidinone analogues were synthesized with considerable variation at the P and P' sites. The cyclopentanone and 2-pyrrolidinone analogues 45 and 57 showed low nM BACE inhibition. X-ray cocrystal structures of two analogues 5 and 45 revealed excellent convergence with the original inhibitor 1 structure while providing new insights into other interactions which could be exploited for future modifications.
-===Crystal structure of human beta secretase complexed with NVP-AMK640===
+Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics.,Hanessian S, Yun H, Hou Y, Yang G, Bayrakdarian M, Therrien E, Moitessier N, Roggo S, Veenstra S, Tintelnot-Blomley M, Rondeau JM, Ostermeier C, Strauss A, Ramage P, Paganetti P, Neumann U, Betschart C J Med Chem. 2005 Aug 11;48(16):5175-90. PMID:16078837<ref>PMID:16078837</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1ym4" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_16078837}}, 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 16078837 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_16078837}}
+__TOC__
+</StructureSection>
-==About this Structure==
-YM4 is a [[Single protein]] 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=1YM4 OCA].
-==Reference==
-Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics., Hanessian S, Yun H, Hou Y, Yang G, Bayrakdarian M, Therrien E, Moitessier N, Roggo S, Veenstra S, Tintelnot-Blomley M, Rondeau JM, Ostermeier C, Strauss A, Ramage P, Paganetti P, Neumann U, Betschart C, J Med Chem. 2005 Aug 11;48(16):5175-90. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16078837 16078837]
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Bayrakdarian M]]
-[[Category: Bayrakdarian, M.]]
+[[Category: Hanessian S]]
-[[Category: Hanessian, S.]]
+[[Category: Hou Y]]
-[[Category: Hou, Y.]]
+[[Category: Moitessier N]]
-[[Category: Moitessier, N.]]
+[[Category: Roggo S]]
-[[Category: Roggo, S.]]
+[[Category: Therrien E]]
-[[Category: Therrien, E.]]
+[[Category: Veenstra S]]
-[[Category: Veenstra, S.]]
+[[Category: Yang G]]
-[[Category: Yang, G.]]
+[[Category: Yun H]]
-[[Category: Yun, H.]]
-[[Category: Alzheimer's disease]]
-[[Category: Aspartic protease]]
-[[Category: Beta-secretase]]
-[[Category: Memapsin2]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 01:12:28 2008''