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==Crystal structure of the PH-TH module of Bruton's tyrosine kinase bound to inositol hexakisphosphate==
==Crystal structure of the PH-TH module of Bruton's tyrosine kinase bound to inositol hexakisphosphate==
<StructureSection load='4y94' size='340' side='right' caption='[[4y94]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
<StructureSection load='4y94' size='340' side='right'caption='[[4y94]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4y94]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y94 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y94 FirstGlance]. <br>
<table><tr><td colspan='2'>[[4y94]] 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=4Y94 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y94 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4y93|4y93]], [[4y95|4y95]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IHP:INOSITOL+HEXAKISPHOSPHATE'>IHP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<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>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4y94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y94 OCA], [https://pdbe.org/4y94 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y94 RCSB], [https://www.ebi.ac.uk/pdbsum/4y94 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y94 ProSAT]</span></td></tr>
<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=4y94 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y94 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y94 RCSB], [http://www.ebi.ac.uk/pdbsum/4y94 PDBsum]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/Q3ZC95_BOVIN Q3ZC95_BOVIN]
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.
 
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>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==See Also==
</div>
*[[Tyrosine kinase 3D structures|Tyrosine kinase 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Non-specific protein-tyrosine kinase]]
[[Category: Bos taurus]]
[[Category: Kuriyan, J]]
[[Category: Large Structures]]
[[Category: Wang, Q]]
[[Category: Kuriyan J]]
[[Category: Btk]]
[[Category: Wang Q]]
[[Category: Inositol hexakisphosphate]]
[[Category: Ph domain]]
[[Category: Transferase]]
[[Category: Tyrosine kinase]]

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