8r18: Difference between revisions
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==Pim1 in complex with (E)-4-(4-hydroxystyryl)benzoic acid and Pimtide== | |||
<StructureSection load='8r18' size='340' side='right'caption='[[8r18]], [[Resolution|resolution]] 1.89Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8r18]] is a 2 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=8R18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R18 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]] 1.89Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=XGK:(E)-4-(4-hydroxystyryl)benzoic+acid'>XGK</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=8r18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r18 OCA], [https://pdbe.org/8r18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r18 RCSB], [https://www.ebi.ac.uk/pdbsum/8r18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r18 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Recently, we have developed novel Pim-1 kinase inhibitors starting from a dihydrobenzofuran core structure using a computational approach. Here, we report the design and synthesis of stilbene-based Pim-1 kinase inhibitors obtained by formal elimination of the dihydrofuran ring. These inhibitors of the first design cycle, which were obtained as inseparable cis/trans mixtures, showed affinities in the low single-digit micromolar range. To be able to further optimize these compounds in a structure-based fashion, we determined the X-ray structures of the protein-ligand-complexes. Surprisingly, only the cis-isomer binds upon crystallization of the cis/trans-mixture of the ligands with Pim-1 kinase and the substrate PIMTIDE, the binding mode being largely consistent with that predicted by docking. After crystallization of the exclusively trans-configured derivatives, a markedly different binding mode for the inhibitor and a concomitant rearrangement of the glycine-rich loop is observed, resulting in the ligand being deeply buried in the binding pocket. | |||
What doesn't fit is made to fit: Pim-1 kinase adapts to the configuration of stilbene-based inhibitors.,Hochban PMM, Heyder L, Heine A, Diederich WE Arch Pharm (Weinheim). 2024 Jun;357(6):e2400094. doi: 10.1002/ardp.202400094. , Epub 2024 Apr 17. PMID:38631036<ref>PMID:38631036</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8r18" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Diederich WE]] | |||
[[Category: Heine A]] | |||
[[Category: Hochban PMM]] | |||
Latest revision as of 05:26, 12 June 2024
Pim1 in complex with (E)-4-(4-hydroxystyryl)benzoic acid and Pimtide
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