8jot: Difference between revisions
New page: '''Unreleased structure''' The entry 8jot is ON HOLD Authors: Description: Category: Unreleased Structures |
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==Crystal structure of CSF-1R kinase domain with sulfatinib== | |||
<StructureSection load='8jot' size='340' side='right'caption='[[8jot]], [[Resolution|resolution]] 1.69Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8jot]] is a 1 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=8JOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8JOT 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]] 1.69Å</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=UKI:~{N}-[2-(dimethylamino)ethyl]-1-[3-[[4-[(2-methyl-1~{H}-indol-5-yl)oxy]pyrimidin-2-yl]amino]phenyl]methanesulfonamide'>UKI</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=8jot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8jot OCA], [https://pdbe.org/8jot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8jot RCSB], [https://www.ebi.ac.uk/pdbsum/8jot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8jot ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Acquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1R(T663I). This study not only sheds light on the structural basis governing sulfatinib's FGFR/CSF-1R inhibition, but also provides valuable insights into the rational design of dual- or multi-target FGFR inhibitors with selectivity for CSF-1R and sensitivity to gatekeeper mutations. | |||
Structural basis and selectivity of sulfatinib binding to FGFR and CSF-1R.,Lin Q, Dai S, Qu L, Lin H, Guo M, Wei H, Chen Y, Chen X Commun Chem. 2024 Jan 3;7(1):3. doi: 10.1038/s42004-023-01084-0. PMID:38172256<ref>PMID:38172256</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8jot" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen XJ]] | |||
[[Category: Chen YH]] | |||
[[Category: Lin QM]] | |||
Latest revision as of 10:30, 21 November 2024
Crystal structure of CSF-1R kinase domain with sulfatinibCrystal structure of CSF-1R kinase domain with sulfatinib
Structural highlights
Publication Abstract from PubMedAcquired drug resistance poses a challenge for single-target FGFR inhibitors, leading to the development of dual- or multi-target FGFR inhibitors. Sulfatinib is a multi-target kinase inhibitor for treating neuroendocrine tumors, selectively targeting FGFR1/CSF-1R. To elucidate the molecular mechanisms behind its binding and kinase selectivity, we determined the crystal structures of sulfatinib with FGFR1/CSF-1R. The results reveal common structural features and distinct conformational adaptability of sulfatinib in response to FGFR1/CSF-1R binding. Further biochemical and structural analyses disclose sensitivity of sulfatinib to FGFR/CSF-1R gatekeeper mutations. The insensitivity of sulfatinib to FGFR gatekeeper mutations highlights the indispensable interactions with the hydrophobic pocket for FGFR selectivity, whereas the rotatory flexibility may enable sulfatinib to overcome CSF-1R(T663I). This study not only sheds light on the structural basis governing sulfatinib's FGFR/CSF-1R inhibition, but also provides valuable insights into the rational design of dual- or multi-target FGFR inhibitors with selectivity for CSF-1R and sensitivity to gatekeeper mutations. Structural basis and selectivity of sulfatinib binding to FGFR and CSF-1R.,Lin Q, Dai S, Qu L, Lin H, Guo M, Wei H, Chen Y, Chen X Commun Chem. 2024 Jan 3;7(1):3. doi: 10.1038/s42004-023-01084-0. PMID:38172256[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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