2x39: Difference between revisions

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-[[Image:2x39.png|left|200px]]
-<!--
+==Structure of 4-Amino-N-(4-chlorobenzyl)-1-(7H-pyrrolo(2,3-d)pyrimidin- 4-yl)piperidine-4-carboxamide bound to PKB==
-The line below this paragraph, containing "STRUCTURE_2x39", creates the "Structure Box" on the page.
+<StructureSection load='2x39' size='340' side='right'caption='[[2x39]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2x39]] is a 2 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=2X39 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X39 FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.93&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene>, <scene name='pdbligand=X39:4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE'>X39</scene></td></tr>
-{{STRUCTURE_2x39|  PDB=2x39  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2x39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x39 OCA], [https://pdbe.org/2x39 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x39 RCSB], [https://www.ebi.ac.uk/pdbsum/2x39 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x39 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/x3/2x39_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=2x39 ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Protein kinase B (PKB or Akt) is an important component of intracellular signaling pathways regulating growth and survival. Signaling through PKB is frequently deregulated in cancer, and inhibitors of PKB therefore have potential as antitumor agents. The optimization of lipophilic substitution within a series of 4-benzyl-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-amines provided ATP-competitive, nanomolar inhibitors with up to 150-fold selectivity for inhibition of PKB over the closely related kinase PKA. Although active in cellular assays, compounds containing 4-amino-4-benzylpiperidines underwent metabolism in vivo, leading to rapid clearance and low oral bioavailability. Variation of the linker group between the piperidine and the lipophilic substituent identified 4-amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides as potent and orally bioavailable inhibitors of PKB. Representative compounds modulated biomarkers of signaling through PKB in vivo and strongly inhibited the growth of human tumor xenografts in nude mice at well-tolerated doses.
-===STRUCTURE OF 4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO(2,3-D) PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE BOUND TO PKB===
+Discovery of 4-Amino-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamides As Selective, Orally Active Inhibitors of Protein Kinase B (Akt).,McHardy T, Caldwell JJ, Cheung KM, Hunter LJ, Taylor K, Rowlands M, Ruddle R, Henley A, de Haven Brandon A, Valenti M, Davies TG, Fazal L, Seavers L, Raynaud FI, Eccles SA, Aherne GW, Garrett MD, Collins I J Med Chem. 2010 Feb 12. PMID:20151677<ref>PMID:20151677</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2x39" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_20151677}}, adds the Publication Abstract to the page
+*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 20151677 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_20151677}}
+__TOC__
+</StructureSection>
-==About this Structure==
-[[2x39]] is a 2 chain structure with 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=2X39 OCA].
-==Reference==
-<ref group="xtra">PMID:020151677</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Non-specific serine/threonine protein kinase]]
+[[Category: Large Structures]]
-[[Category: Aherne, G W.]]
+[[Category: Aherne GW]]
-[[Category: Brandon, A D.]]
+[[Category: Brandon AD]]
-[[Category: Caldwell, J J.]]
+[[Category: Caldwell JJ]]
-[[Category: Cheung, K M.]]
+[[Category: Cheung KM]]
-[[Category: Collins, I.]]
+[[Category: Collins I]]
-[[Category: Davies, T G.]]
+[[Category: Davies TG]]
-[[Category: Eccles, S A.]]
+[[Category: Eccles SA]]
-[[Category: Fazal, L.]]
+[[Category: Fazal L]]
-[[Category: Garrett, M D.]]
+[[Category: Garrett MD]]
-[[Category: Henley, A.]]
+[[Category: Henley A]]
-[[Category: Hunter, L J.]]
+[[Category: Hunter LJ]]
-[[Category: Mchardy, T.]]
+[[Category: McHardy T]]
-[[Category: Raynaud, F I.]]
+[[Category: Raynaud FI]]
-[[Category: Rowlands, M.]]
+[[Category: Rowlands M]]
-[[Category: Ruddle, R.]]
+[[Category: Ruddle R]]
-[[Category: Seavers, L.]]
+[[Category: Seavers L]]
-[[Category: Taylor, K.]]
+[[Category: Taylor K]]
-[[Category: Valenti, M.]]
+[[Category: Valenti M]]
-[[Category: Kinase]]
-[[Category: Nucleotide-binding]]
-[[Category: Phosphoprotein]]
-[[Category: Serine/threonine-protein kinase]]
-[[Category: Transferase]]
-[[Category: Wnt signaling pathway]]