8r1t
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Pim1 in complex with 4-(4-aminophenethyl)benzoic acid and Pimtide== | |
| + | <StructureSection load='8r1t' size='340' side='right'caption='[[8r1t]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8r1t]] 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=8R1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8R1T 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]] 2Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=XIJ:4-(4-aminophenethyl)benzoic+acid'>XIJ</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=8r1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8r1t OCA], [https://pdbe.org/8r1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8r1t RCSB], [https://www.ebi.ac.uk/pdbsum/8r1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8r1t 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 8r1t" 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]] | ||
Current revision
Pim1 in complex with 4-(4-aminophenethyl)benzoic acid and Pimtide
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