1xs7: Difference between revisions
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New page: left|200px<br /> <applet load="1xs7" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xs7, resolution 2.8Å" /> '''Crystal Structure of... |
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== | ==Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).== | ||
A series of novel macrocyclic amide-urethanes was designed and synthesized | <StructureSection load='1xs7' size='340' side='right'caption='[[1xs7]], [[Resolution|resolution]] 2.80Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1xs7]] 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=1XS7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XS7 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MMI:N-[(4S,5S,7R)-8-({(S)-1-[(BENZYLAMINO)OXOMETHYL]-2-METHYLPROPYL}AMINO)-5-HYDROXY-2,7-DIMETHYL-8-OXO-OCT-4-YL]-(4S,7S)-4-ISOPROPYL-2,5,9-TRIOXO-1-OXA-3,6,10-TRIAZACYCLOHEXADECANE-7-CARBOXAMIDE'>MMI</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1xs7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xs7 OCA], [https://pdbe.org/1xs7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xs7 RCSB], [https://www.ebi.ac.uk/pdbsum/1xs7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xs7 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/xs/1xs7_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/main_output.php?pdb_ID=1xs7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase). | |||
Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).,Ghosh AK, Devasamudram T, Hong L, DeZutter C, Xu X, Weerasena V, Koelsch G, Bilcer G, Tang J Bioorg Med Chem Lett. 2005 Jan 3;15(1):15-20. PMID:15582402<ref>PMID:15582402</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1xs7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta secretase 3D structures|Beta secretase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bilcer G]] | |||
[[Category: Bilcer | [[Category: DeZutter C]] | ||
[[Category: DeZutter | [[Category: Devasamudram T]] | ||
[[Category: Devasamudram | [[Category: Ghosh A]] | ||
[[Category: Ghosh | [[Category: Hong L]] | ||
[[Category: Hong | [[Category: Koelsch G]] | ||
[[Category: Koelsch | [[Category: Tang J]] | ||
[[Category: Tang | [[Category: Weerasena V]] | ||
[[Category: Weerasena | [[Category: Xu X]] | ||
[[Category: Xu | |||
Latest revision as of 06:48, 23 August 2023
Crystal Structure of a cycloamide-urethane-derived novel inhibitor bound to human brain memapsin 2 (beta-secretase).
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