3wzd: Difference between revisions
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==KDR in complex with ligand lenvatinib== | |||
<StructureSection load='3wzd' size='340' side='right'caption='[[3wzd]], [[Resolution|resolution]] 1.57Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3wzd]] 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=3WZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WZD 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]] 1.57Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DTT:2,3-DIHYDROXY-1,4-DITHIOBUTANE'>DTT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LEV:4-{3-CHLORO-4-[(CYCLOPROPYLCARBAMOYL)AMINO]PHENOXY}-7-METHOXYQUINOLINE-6-CARBOXAMIDE'>LEV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3wzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3wzd OCA], [https://pdbe.org/3wzd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3wzd RCSB], [https://www.ebi.ac.uk/pdbsum/3wzd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3wzd ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lenvatinib is an oral multikinase inhibitor that selectively inhibits vascular endothelial growth factor (VEGF) receptors 1 to 3 and other proangiogenic and oncogenic pathway-related receptor tyrosine kinases. To elucidate the origin of the potency of lenvatinib in VEGF receptor 2 (VEGFR2) inhibition, we conducted a kinetic interaction analysis of lenvatinib with VEGFR2 and X-ray analysis of the crystal structure of VEGFR2-lenvatinib complexes. Kinetic analysis revealed that lenvatinib had a rapid association rate constant and a relatively slow dissociation rate constant in complex with VEGFR2. Co-crystal structure analysis demonstrated that lenvatinib binds at its ATP mimetic quinoline moiety to the ATP binding site and to the neighboring region via a cyclopropane ring, adopting an Asp-Phe-Gly (DFG)-"in" conformation. These results suggest that lenvatinib is very distinct in its binding mode of interaction compared to the several approved VEGFR2 kinase inhibitors. | |||
Distinct binding mode of multikinase inhibitor lenvatinib revealed by biochemical characterization.,Okamoto K, Ikemori-Kawada M, Jestel A, von Konig K, Funahashi Y, Matsushima T, Tsuruoka A, Inoue A, Matsui J ACS Med Chem Lett. 2014 Nov 17;6(1):89-94. doi: 10.1021/ml500394m. eCollection, 2015 Jan 8. PMID:25589937<ref>PMID:25589937</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 3wzd" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: Matsui | *[[3D structures of vascular endothelial growth factor receptor|3D structures of vascular endothelial growth factor receptor]] | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ikemori_Kawada M]] | |||
[[Category: Inoue A]] | |||
[[Category: Matsui J]] | |||
[[Category: Okamoto K]] | |||