2dq7

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[[Image:2dq7.gif|left|200px]]
 
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==Crystal Structure of Fyn kinase domain complexed with staurosporine==
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The line below this paragraph, containing "STRUCTURE_2dq7", creates the "Structure Box" on the page.
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<StructureSection load='2dq7' size='340' side='right'caption='[[2dq7]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2dq7]] 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=2DQ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2DQ7 FirstGlance]. <br>
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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]] 2.8&#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=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</scene></td></tr>
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{{STRUCTURE_2dq7| PDB=2dq7 | SCENE= }}
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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=2dq7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2dq7 OCA], [https://pdbe.org/2dq7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2dq7 RCSB], [https://www.ebi.ac.uk/pdbsum/2dq7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2dq7 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/FYN_HUMAN FYN_HUMAN] Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1.<ref>PMID:7822789</ref> <ref>PMID:7568038</ref> <ref>PMID:11005864</ref> <ref>PMID:11162638</ref> <ref>PMID:11536198</ref> <ref>PMID:12788081</ref> <ref>PMID:12640114</ref> <ref>PMID:14761972</ref> <ref>PMID:15557120</ref> <ref>PMID:14707117</ref> <ref>PMID:15536091</ref> <ref>PMID:16387660</ref> <ref>PMID:16841086</ref> <ref>PMID:17194753</ref> <ref>PMID:18056706</ref> <ref>PMID:18258597</ref> <ref>PMID:19179337</ref> <ref>PMID:19652227</ref> <ref>PMID:20100835</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/dq/2dq7_consurf.spt"</scriptWhenChecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2dq7 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The tyrosine kinase Fyn is a member of the Src kinase family. Besides the role of Fyn in T cell signal transduction in concert with Lck, its excess activity in the brain is involved with conditions such as Alzheimer's and Parkinson's diseases. Therefore, inhibition of Fyn kinase may help counteract these nervous system disorders. Here, we solved the crystal structure of the human Fyn kinase domain complexed with staurosporine, a potent kinase inhibitor, at 2.8 A resolution. Staurosporine binds to the ATP-binding site of Fyn in a similar manner as in the Lck- and Csk-complexes. The small structural differences in the staurosporine-binding and/or -unbinding region among the three kinase domains may help obtaining the selective inhibitors against the respective kinases.
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'''Crystal Structure of Fyn kinase domain complexed with staurosporine'''
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Structure of human Fyn kinase domain complexed with staurosporine.,Kinoshita T, Matsubara M, Ishiguro H, Okita K, Tada T Biochem Biophys Res Commun. 2006 Aug 4;346(3):840-4. Epub 2006 Jun 13. PMID:16782058<ref>PMID:16782058</ref>
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==Overview==
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The tyrosine kinase Fyn is a member of the Src kinase family. Besides the role of Fyn in T cell signal transduction in concert with Lck, its excess activity in the brain is involved with conditions such as Alzheimer's and Parkinson's diseases. Therefore, inhibition of Fyn kinase may help counteract these nervous system disorders. Here, we solved the crystal structure of the human Fyn kinase domain complexed with staurosporine, a potent kinase inhibitor, at 2.8 A resolution. Staurosporine binds to the ATP-binding site of Fyn in a similar manner as in the Lck- and Csk-complexes. The small structural differences in the staurosporine-binding and/or -unbinding region among the three kinase domains may help obtaining the selective inhibitors against the respective kinases.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2DQ7 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2DQ7 OCA].
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</div>
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<div class="pdbe-citations 2dq7" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Structure of human Fyn kinase domain complexed with staurosporine., Kinoshita T, Matsubara M, Ishiguro H, Okita K, Tada T, Biochem Biophys Res Commun. 2006 Aug 4;346(3):840-4. Epub 2006 Jun 13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16782058 16782058]
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*[[Tyrosine kinase|Tyrosine kinase]]
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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__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific protein-tyrosine kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Kinoshita T]]
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[[Category: Kinoshita, T.]]
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[[Category: Tada T]]
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[[Category: Tada, T.]]
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[[Category: Kinase domain]]
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[[Category: Src family]]
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[[Category: Staurosporine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 00:57:11 2008''
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Current revision

Crystal Structure of Fyn kinase domain complexed with staurosporine

PDB ID 2dq7

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