4n1b: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4n1b]] is a 3 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=4N1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N1B FirstGlance]. <br> | <table><tr><td colspan='2'>[[4n1b]] is a 3 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=4N1B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4N1B FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FS:(1S,2R)-2-{[(1S)-1-[(1-OXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)METHYL]-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]CARBONYL}CYCLOHEXANECARBOXYLIC+ACID'>2FS</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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]] 2.55Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2FS:(1S,2R)-2-{[(1S)-1-[(1-OXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)METHYL]-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]CARBONYL}CYCLOHEXANECARBOXYLIC+ACID'>2FS</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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=4n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n1b OCA], [https://pdbe.org/4n1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n1b RCSB], [https://www.ebi.ac.uk/pdbsum/4n1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n1b ProSAT]</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=4n1b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n1b OCA], [https://pdbe.org/4n1b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4n1b RCSB], [https://www.ebi.ac.uk/pdbsum/4n1b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4n1b ProSAT]</span></td></tr> | ||
</table> | </table> | ||
Latest revision as of 09:43, 17 October 2024
STRUCTURE OF KEAP1 KELCH DOMAIN WITH(1S,2R)-2-[(1S)-1-[(1-oxo-2,3-dihydro-1H-isoindol-2-Yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-Carbonyl]cyclohexane-1-carboxylic acidSTRUCTURE OF KEAP1 KELCH DOMAIN WITH(1S,2R)-2-[(1S)-1-[(1-oxo-2,3-dihydro-1H-isoindol-2-Yl)methyl]-1,2,3,4-tetrahydroisoquinoline-2-Carbonyl]cyclohexane-1-carboxylic acid
Structural highlights
FunctionPublication Abstract from PubMedAn X-ray crystal structure of Kelch-like ECH-associated protein (Keap1) co-crystallised with (1S,2R)-2-[(1S)-1-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-1,2,3,4-tetrah ydroisoquinolin-2-carbonyl]cyclohexane-1-carboxylic acid (compound (S,R,S)-1 a) was obtained. This X-ray crystal structure provides breakthrough experimental evidence for the true binding mode of the hit compound (S,R,S)-1 a, as the ligand orientation was found to differ from that of the initial docking model, which was available at the start of the project. Crystallographic elucidation of this binding mode helped to focus and drive the drug design process more effectively and efficiently. Binding Mode and Structure-Activity Relationships around Direct Inhibitors of the Nrf2-Keap1 Complex.,Jnoff E, Albrecht C, Barker JJ, Barker O, Beaumont E, Bromidge S, Brookfield F, Brooks M, Bubert C, Ceska T, Corden V, Dawson G, Duclos S, Fryatt T, Genicot C, Jigorel E, Kwong J, Maghames R, Mushi I, Pike R, Sands ZA, Smith MA, Stimson CC, Courade JP ChemMedChem. 2014 Feb 6. doi: 10.1002/cmdc.201300525. PMID:24504667[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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