2v00: Difference between revisions
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==X-ray crystal structure of endothiapepsin complexed with compound 1== | |||
<StructureSection load='2v00' size='340' side='right'caption='[[2v00]], [[Resolution|resolution]] 1.55Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2v00]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V00 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V00 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]] 1.55Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=V15:2-AMINO-6-(2-PHENYLETHYL)PYRIMIDIN-4(3H)-ONE'>V15</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=2v00 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v00 OCA], [https://pdbe.org/2v00 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v00 RCSB], [https://www.ebi.ac.uk/pdbsum/2v00 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v00 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA] | |||
== 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/v0/2v00_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=2v00 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Fragment-based lead generation was applied to find novel small-molecule inhibitors of beta-secretase (BACE-1), a key target for the treatment of Alzheimer's disease. Fragment hits coming from a 1D NMR screen were characterized by BIAcore, and the most promising compounds were soaked into protein crystals to help the rational design of more potent hit analogues. Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead against BACE-1, and the accompanying paper in this journal describes how these were optimized to a lead series of nanomolar inhibitors.1. | |||
Discovery of a novel warhead against beta-secretase through fragment-based lead generation.,Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861<ref>PMID:17985861</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2v00" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Pepsin|Pepsin]] | *[[Pepsin|Pepsin]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Cryphonectria parasitica]] | [[Category: Cryphonectria parasitica]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Albert | [[Category: Albert JS]] | ||
[[Category: Beer | [[Category: De Beer T]] | ||
[[Category: Deinum | [[Category: Deinum J]] | ||
[[Category: Edwards | [[Category: Edwards PD]] | ||
[[Category: Folmer | [[Category: Folmer RHA]] | ||
[[Category: Geschwindner | [[Category: Geschwindner S]] | ||
[[Category: Olsson | [[Category: Olsson LL]] | ||
Latest revision as of 17:59, 13 December 2023
X-ray crystal structure of endothiapepsin complexed with compound 1X-ray crystal structure of endothiapepsin complexed with compound 1
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedFragment-based lead generation was applied to find novel small-molecule inhibitors of beta-secretase (BACE-1), a key target for the treatment of Alzheimer's disease. Fragment hits coming from a 1D NMR screen were characterized by BIAcore, and the most promising compounds were soaked into protein crystals to help the rational design of more potent hit analogues. Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead against BACE-1, and the accompanying paper in this journal describes how these were optimized to a lead series of nanomolar inhibitors.1. Discovery of a novel warhead against beta-secretase through fragment-based lead generation.,Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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