1xn3: Difference between revisions

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-{{Seed}}
-[[Image:1xn3.png|left|200px]]
-<!--
+==Crystal structure of Beta-secretase bound to a long inhibitor with additional upstream residues.==
-The line below this paragraph, containing "STRUCTURE_1xn3", creates the "Structure Box" on the page.
+<StructureSection load='1xn3' size='340' side='right'caption='[[1xn3]], [[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'>[[1xn3]] is a 5 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=1XN3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XN3 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=STA:STATINE'>STA</scene></td></tr>
-{{STRUCTURE_1xn3|  PDB=1xn3  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xn3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xn3 OCA], [https://pdbe.org/1xn3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xn3 RCSB], [https://www.ebi.ac.uk/pdbsum/1xn3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xn3 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/xn/1xn3_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=1xn3 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Memapsin 2 (beta-secretase) is the membrane-anchored aspartic protease that initiates the cleavage of beta-amyloid precursor protein (APP), leading to the production of amyloid-beta (Abeta), a major factor in the pathogenesis of Alzheimer's disease. The active site of memapsin 2 has been shown, with kinetic data and crystal structures, to bind to eight substrate residues (P(4)-P(4)'). We describe here that the addition of three substrate residues from P(7) to P(5) strongly influences the hydrolytic activity by memapsin 2 and these subsites prefer hydrophobic residues, especially tryptophan. A crystal structure of memapsin 2 complexed with a statine-based inhibitor spanning P(10)-P(4)' revealed the binding positions of P(5)-P(7) residues. Kinetic studies revealed that the addition of these substrate residues contributes to the decrease in K(m) and increase in k(cat) values, suggesting that these residues contribute to both substrate recognition and transition-state binding. The crystal structure of a new inhibitor, OM03-4 (K(i) = 0.03 nM), bound to memapsin 2 revealed the interaction of a tryptophan with the S(6) subsite of the protease.
-===Crystal structure of Beta-secretase bound to a long inhibitor with additional upstream residues.===
+Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase).,Turner RT 3rd, Hong L, Koelsch G, Ghosh AK, Tang J Biochemistry. 2005 Jan 11;44(1):105-12. PMID:15628850<ref>PMID:15628850</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1xn3" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_15628850}}, 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 15628850 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_15628850}}
+__TOC__
+</StructureSection>
-==About this Structure==
-XN3 is a 5 chains structure of sequences 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=1XN3 OCA].
-==Reference==
-<ref group="xtra">PMID:15628850</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Ghosh, A K.]]
+[[Category: Ghosh AK]]
-[[Category: Hong, L.]]
+[[Category: Hong L]]
-[[Category: III, R T.Turner.]]
+[[Category: Koelsch G]]
-[[Category: Koelsch, G.]]
+[[Category: Tang J]]
-[[Category: Tang, J.]]
+[[Category: Turner III RT]]
-[[Category: Alzheimer's disease]]
-[[Category: Asp2]]
-[[Category: Aspartic protease]]
-[[Category: Bace]]
-[[Category: Beta secretase]]
-[[Category: Drug design]]
-[[Category: Memapsin2]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 09:22:38 2009''