5mb0: Difference between revisions

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<StructureSection load='5mb0' size='340' side='right'caption='[[5mb0]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
<StructureSection load='5mb0' size='340' side='right'caption='[[5mb0]], [[Resolution|resolution]] 1.15&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[5mb0]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MB0 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MB0 FirstGlance]. <br>
<table><tr><td colspan='2'>[[5mb0]] 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=5MB0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MB0 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=47V:2,5-DIMETHYL-N-(PYRIDIN-4-YL)FURAN-3-CARBOXAMIDE'>47V</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=F63:N-METHYL-1-[5-(PYRIDIN-3-YLOXY)FURAN-2-YL]METHANAMINE'>F63</scene>, <scene name='pdbligand=F91:N-(PYRIDIN-4-YLMETHYL)-2,3-DIHYDRO-1,4-BENZODIOXIN-6-AMINE'>F91</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.149&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t7p|3t7p]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=47V:2,5-DIMETHYL-N-(PYRIDIN-4-YL)FURAN-3-CARBOXAMIDE'>47V</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=F63:N-METHYL-1-[5-(PYRIDIN-3-YLOXY)FURAN-2-YL]METHANAMINE'>F63</scene>, <scene name='pdbligand=F91:N-(PYRIDIN-4-YLMETHYL)-2,3-DIHYDRO-1,4-BENZODIOXIN-6-AMINE'>F91</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] </span></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=5mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mb0 OCA], [https://pdbe.org/5mb0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mb0 RCSB], [https://www.ebi.ac.uk/pdbsum/5mb0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mb0 ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mb0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mb0 OCA], [http://pdbe.org/5mb0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mb0 RCSB], [http://www.ebi.ac.uk/pdbsum/5mb0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mb0 ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/CARP_CRYPA CARP_CRYPA]
Crystallography is frequently used as follow-up method to validate hits identified by biophysical screening cascades. The capacity of crystallography to directly screen fragment libraries is often underestimated, due to its supposed low-throughput and need for high-quality crystals. We applied crystallographic fragment screening to map the protein-binding site of the aspartic protease endothiapepsin by individual soaking experiments. Here, we report on 41 fragments binding to the catalytic dyad and adjacent specificity pockets. The analysis identifies already known warheads but also reveals hydrazide, pyrazole, or carboxylic acid fragments as novel functional groups binding to the dyad. A remarkable swapping of the S1 and S1' pocket between structurally related fragments is explained by either steric demand, required displacement of a well-bound water molecule, or changes of trigonal-planar to tetrahedral geometry of an oxygen functional group in a side chain. Some warheads simultaneously occupying both S1 and S1' are promising starting points for fragment-growing strategies.


Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads To Address a Catalytic Dyad.,Radeva N, Schiebel J, Wang X, Krimmer SG, Fu K, Stieler M, Ehrmann FR, Metz A, Rickmeyer T, Betz M, Winquist J, Park AY, Huschmann FU, Weiss MS, Mueller U, Heine A, Klebe G J Med Chem. 2016 Nov 10;59(21):9743-9759. doi: 10.1021/acs.jmedchem.6b01195. Epub, 2016 Oct 28. PMID:27726357<ref>PMID:27726357</ref>
==See Also==
 
*[[Pepsin|Pepsin]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mb0" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cryphonectria parasitica]]
[[Category: Cryphonectria parasitica]]
[[Category: Endothiapepsin]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Heine, A]]
[[Category: Heine A]]
[[Category: Klebe, G]]
[[Category: Klebe G]]
[[Category: Radeva, N]]
[[Category: Radeva N]]
[[Category: Fragment cocktail screening]]
[[Category: Hydrolase]]
[[Category: Inhibition]]

Latest revision as of 21:35, 1 November 2023

Cocktail experiment A: fragments 63, 267, and 291 in complex with EndothiapepsinCocktail experiment A: fragments 63, 267, and 291 in complex with Endothiapepsin

Structural highlights

5mb0 is a 1 chain structure with sequence from Cryphonectria parasitica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.149Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CARP_CRYPA

See Also

5mb0, resolution 1.15Å

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OCA
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