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4y95

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==Crystal structure of the kinase domain of Bruton's tyrosine kinase with mutations in the activation loop==
==Crystal structure of the kinase domain of Bruton's tyrosine kinase with mutations in the activation loop==
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<StructureSection load='4y95' size='340' side='right' caption='[[4y95]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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<StructureSection load='4y95' size='340' side='right'caption='[[4y95]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4y95]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y95 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y95 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4y95]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y95 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y95 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=746:4-TERT-BUTYL-N-[2-METHYL-3-(4-METHYL-6-{[4-(MORPHOLIN-4-YLCARBONYL)PHENYL]AMINO}-5-OXO-4,5-DIHYDROPYRAZIN-2-YL)PHENYL]BENZAMIDE'>746</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></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]] 1.599&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4y93|4y93]], [[4y94|4y94]]</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=746:4-TERT-BUTYL-N-[2-METHYL-3-(4-METHYL-6-{[4-(MORPHOLIN-4-YLCARBONYL)PHENYL]AMINO}-5-OXO-4,5-DIHYDROPYRAZIN-2-YL)PHENYL]BENZAMIDE'>746</scene>, <scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span></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=4y95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y95 OCA], [https://pdbe.org/4y95 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y95 RCSB], [https://www.ebi.ac.uk/pdbsum/4y95 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y95 ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4y95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y95 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y95 RCSB], [http://www.ebi.ac.uk/pdbsum/4y95 PDBsum]</span></td></tr>
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</table>
</table>
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<div style="background-color:#fffaf0;">
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== Function ==
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== Publication Abstract from PubMed ==
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[https://www.uniprot.org/uniprot/Q3ZC95_BOVIN Q3ZC95_BOVIN]
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Bruton's tyrosine kinase (Btk), a Tec-family tyrosine kinase, is essential for B-cell function. We present crystallographic and biochemical analyses of Btk, which together reveal molecular details of its autoinhibition and activation. Autoinhibited Btk adopts a compact conformation like that of inactive c-Src and c-Abl. A lipid-binding PH-TH module, unique to Tec kinases, acts in conjunction with the SH2 and SH3 domains to stabilize the inactive conformation. In addition to the expected activation of Btk by membranes containing phosphatidylinositol triphosphate (PIP3), we found that inositol hexakisphosphate (IP6), a soluble signaling molecule found in both animal and plant cells, also activates Btk. This activation is a consequence of a transient PH-TH dimerization induced by IP6, which promotes transphosphorylation of the kinase domains. Sequence comparisons with other Tec-family kinases suggest that activation by IP6 is unique to Btk.
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Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate.,Wang Q, Vogan EM, Nocka LM, Rosen CE, Zorn JA, Harrison SC, Kuriyan J Elife. 2015 Feb 20;4. doi: 10.7554/eLife.06074. PMID:25699547<ref>PMID:25699547</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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==See Also==
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</div>
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*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Non-specific protein-tyrosine kinase]]
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[[Category: Bos taurus]]
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[[Category: Kuriyan, J]]
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[[Category: Large Structures]]
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[[Category: Rosen, C E]]
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[[Category: Kuriyan J]]
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[[Category: Wang, Q]]
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[[Category: Rosen CE]]
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[[Category: Btk]]
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[[Category: Wang Q]]
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[[Category: Kinase domain]]
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[[Category: Transferase]]
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Current revision

Crystal structure of the kinase domain of Bruton's tyrosine kinase with mutations in the activation loop

PDB ID 4y95

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