6l8l

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Current revision (10:53, 22 November 2023) (edit) (undo)
 
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==C-Src in complex with ibrutinib==
==C-Src in complex with ibrutinib==
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<StructureSection load='6l8l' size='340' side='right'caption='[[6l8l]]' scene=''>
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<StructureSection load='6l8l' size='340' side='right'caption='[[6l8l]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L8L OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6L8L FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6l8l]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6L8L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6L8L FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6l8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8l OCA], [http://pdbe.org/6l8l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6l8l RCSB], [http://www.ebi.ac.uk/pdbsum/6l8l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8l ProSAT]</span></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.888&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1E8:1-{(3R)-3-[4-AMINO-3-(4-PHENOXYPHENYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL]PIPERIDIN-1-YL}PROP-2-EN-1-ONE'>1E8</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6l8l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6l8l OCA], [https://pdbe.org/6l8l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6l8l RCSB], [https://www.ebi.ac.uk/pdbsum/6l8l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6l8l ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/SRC_CHICK SRC_CHICK] Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process. When cells adhere via focal adhesions to the extra-cellular matrix, signals are transmitted by integrins into the cell and result in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing. Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus.<ref>PMID:1717492</ref> <ref>PMID:8550628</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Ibrutinib is a BTK-targeted irreversible inhibitor. In this study, we demonstrate that ibrutinib potently inhibits SRC activity in a non-covalent manner via mass spectrometry and crystallography. The S345C mutation renders SRC to bind covalently with ibrutinib, and restores the potency of ibrutinib against the gatekeeper mutant. The co-crystal structure of ibrutinib/SRC shows Ser345 of SRC did not form covalent bond with ibrutinib, leading to a decrease of potency and loss of the ability to overcome the gatekeeper mutation of SRC. The X-ray crystallographic studies also provide structural insight into why ibrutinib behaves differently against gatekeeper mutants of different kinases.
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Characterization of ibrutinib as a non-covalent inhibitor of SRC-family kinases.,Guo M, Dai S, Wu D, Duan Y, Li J, Qu L, Jiang L, Chen Z, Chen X, Chen Y Bioorg Med Chem Lett. 2021 Feb 15;34:127757. doi: 10.1016/j.bmcl.2020.127757. , Epub 2020 Dec 24. PMID:33359446<ref>PMID:33359446</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6l8l" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Gallus gallus]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Chen L]]
[[Category: Chen L]]

Current revision

C-Src in complex with ibrutinib

PDB ID 6l8l

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