4l7b: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==Structure of keap1 kelch domain with (1S,2R)-2-{[(1S)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclohexanecarboxylic acid== | |||
<StructureSection load='4l7b' size='340' side='right'caption='[[4l7b]], [[Resolution|resolution]] 2.41Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4l7b]] 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=4L7B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L7B 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]] 2.41Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1VV:(1S,2R)-2-{[(1S)-1-[(1,3-DIOXO-1,3-DIHYDRO-2H-ISOINDOL-2-YL)METHYL]-3,4-DIHYDROISOQUINOLIN-2(1H)-YL]CARBONYL}CYCLOHEXANECARBOXYLIC+ACID'>1VV</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4l7b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l7b OCA], [https://pdbe.org/4l7b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l7b RCSB], [https://www.ebi.ac.uk/pdbsum/4l7b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l7b ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KEAP1_HUMAN KEAP1_HUMAN] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
An 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<ref>PMID:24504667</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4l7b" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Albrecht C]] | |||
[[Category: Barker JJ]] | |||
[[Category: Barker O]] | |||
[[Category: Beaumont E]] | |||
[[Category: Bromidge S]] | |||
[[Category: Brookfield F]] | |||
[[Category: Brooks M]] | |||
[[Category: Ceska T]] | |||
[[Category: Courade JP]] | |||
[[Category: Crabbe T]] | |||
[[Category: Duclos S]] | |||
[[Category: Fryatt T]] | |||
[[Category: Jigorel E]] | |||
[[Category: Jnoff E]] | |||
[[Category: Kwong J]] | |||
[[Category: Sands Z]] | |||
[[Category: Smith MA]] | |||
Latest revision as of 19:13, 20 September 2023
Structure of keap1 kelch domain with (1S,2R)-2-{[(1S)-1-[(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)methyl]-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclohexanecarboxylic 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
|
| ||||||||||||||||||