2v1y: Difference between revisions

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OCA

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-[[Image:2v1y.gif|left|200px]]<br />
-<applet load="2v1y" size="450" color="white" frame="true" align="right" spinBox="true"
-caption="2v1y, resolution 2.40&Aring;" />
-'''STRUCTURE OF A PHOSPHOINOSITIDE 3-KINASE ALPHA ADAPTOR-BINDING DOMAIN (ABD) IN A COMPLEX WITH THE ISH2 DOMAIN FROM P85 ALPHA'''<br />
-==Overview==
+==Structure of a phosphoinositide 3-kinase alpha adaptor-binding domain (ABD) in a complex with the iSH2 domain from p85 alpha==
-Many human cancers involve up-regulation of the phosphoinositide 3-kinase, PI3Kalpha, with oncogenic mutations identified in both the p110alpha, catalytic and the p85alpha regulatory subunits. We used crystallographic, and biochemical approaches to gain insight into activating mutations in, two noncatalytic p110alpha domains-the adaptor-binding and the helical, domains. A structure of the adaptor-binding domain of p110alpha in a, complex with the p85alpha inter-Src homology 2 (inter-SH2) domain shows, that oncogenic mutations in the adaptor-binding domain are not at the, inter-SH2 interface but in a polar surface patch that is a plausible, docking site for other domains in the holo p110/p85 complex. We also, examined helical domain mutations and found that the Glu545 to Lys545, (E545K) oncogenic mutant disrupts an inhibitory charge-charge interaction, with the p85 N-terminal SH2 domain. These studies extend our understanding, of the architecture of PI3Ks and provide insight into how two classes of, mutations that cause a gain in function can lead to cancer.
+<StructureSection load='2v1y' size='340' side='right'caption='[[2v1y]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[2v1y]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V1Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V1Y 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]] 2.4&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=2v1y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v1y OCA], [https://pdbe.org/2v1y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v1y RCSB], [https://www.ebi.ac.uk/pdbsum/2v1y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v1y ProSAT]</span></td></tr>
+</table>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/v1/2v1y_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=2v1y ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Many human cancers involve up-regulation of the phosphoinositide 3-kinase PI3Kalpha, with oncogenic mutations identified in both the p110alpha catalytic and the p85alpha regulatory subunits. We used crystallographic and biochemical approaches to gain insight into activating mutations in two noncatalytic p110alpha domains-the adaptor-binding and the helical domains. A structure of the adaptor-binding domain of p110alpha in a complex with the p85alpha inter-Src homology 2 (inter-SH2) domain shows that oncogenic mutations in the adaptor-binding domain are not at the inter-SH2 interface but in a polar surface patch that is a plausible docking site for other domains in the holo p110/p85 complex. We also examined helical domain mutations and found that the Glu545 to Lys545 (E545K) oncogenic mutant disrupts an inhibitory charge-charge interaction with the p85 N-terminal SH2 domain. These studies extend our understanding of the architecture of PI3Ks and provide insight into how two classes of mutations that cause a gain in function can lead to cancer.
-==About this Structure==
+Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit.,Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL Science. 2007 Jul 13;317(5835):239-42. PMID:17626883<ref>PMID:17626883</ref>
-V1Y is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Active as [http://en.wikipedia.org/wiki/Phosphatidylinositol-4,5-bisphosphate_3-kinase Phosphatidylinositol-4,5-bisphosphate 3-kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.153 2.7.1.153] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2V1Y OCA].
-==Reference==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-Mechanism of two classes of cancer mutations in the phosphoinositide 3-kinase catalytic subunit., Miled N, Yan Y, Hon WC, Perisic O, Zvelebil M, Inbar Y, Schneidman-Duhovny D, Wolfson HJ, Backer JM, Williams RL, Science. 2007 Jul 13;317(5835):239-42. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17626883 17626883]
+</div>
+<div class="pdbe-citations 2v1y" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Phosphoinositide 3-kinase 3D structures|Phosphoinositide 3-kinase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Bos taurus]]
 [[Category: Homo sapiens]]
-[[Category: Phosphatidylinositol-4,5-bisphosphate 3-kinase]]
+[[Category: Large Structures]]
-[[Category: Protein complex]]
+[[Category: Backer JM]]
-[[Category: Backer, J.M.]]
+[[Category: Hon WC]]
-[[Category: Hon, W.C.]]
+[[Category: Inbar Y]]
-[[Category: Inbar, Y.]]
+[[Category: Miled N]]
-[[Category: Miled, N.]]
+[[Category: Perisic O]]
-[[Category: Perisic, O.]]
+[[Category: Schneidman-Duhovny D]]
-[[Category: Schneidman-Duhovny, D.]]
+[[Category: Williams RL]]
-[[Category: Williams, R.L.]]
+[[Category: Wolfson HJ]]
-[[Category: Wolfson, H.J.]]
+[[Category: Yan Y]]
-[[Category: Yan, Y.]]
+[[Category: Zvelebil M]]
-[[Category: Zvelebil, M.]]
-[[Category: alternative splicing]]
-[[Category: cancer]]
-[[Category: disease mutation]]
-[[Category: host-virus interaction]]
-[[Category: kinase]]
-[[Category: oncogenic mutations]]
-[[Category: phosphoinositide]]
-[[Category: phosphoinositide 3-kinase]]
-[[Category: phospholipid]]
-[[Category: phospholipid signalling]]
-[[Category: phosphorylation]]
-[[Category: polymorphism]]
-[[Category: sh2 domain]]
-[[Category: sh3 domain]]
-[[Category: signal transduction]]
-[[Category: transferase]]
-[[Category: ubl conjugation]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:41:42 2007''