2vny

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[[Image:2vny.jpg|left|200px]]
 
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==Structure of PKA-PKB chimera complexed with (1-(9H-Purin-6-yl) piperidin-4-yl)amine==
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The line below this paragraph, containing "STRUCTURE_2vny", creates the "Structure Box" on the page.
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<StructureSection load='2vny' size='340' side='right'caption='[[2vny]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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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'>[[2vny]] 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=2VNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VNY FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 1.96&#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=M02:1-(9H-PURIN-6-YL)PIPERIDIN-4-AMINE'>M02</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
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{{STRUCTURE_2vny| PDB=2vny | 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=2vny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vny OCA], [https://pdbe.org/2vny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vny RCSB], [https://www.ebi.ac.uk/pdbsum/2vny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vny ProSAT]</span></td></tr>
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</table>
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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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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vn/2vny_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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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=2vny 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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Fragment-based screening identified 7-azaindole as a protein kinase B inhibitor scaffold. Fragment elaboration using iterative crystallography of inhibitor-PKA-PKB chimera complexes efficiently guided improvements in the potency and selectivity of the compounds, resulting in the identification of nanomolar 6-(piperidin-1-yl)purine, 4-(piperidin-1-yl)-7-azaindole, and 4-(piperidin-1-yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative activity and showing pathway inhibition in cells. A divergence in the binding mode was seen between 4-aminomethylpiperidine and 4-aminopiperidine containing molecules. Selectivity for PKB vs PKA was observed with 4-aminopiperidine derivatives, and the most PKB-selective inhibitor (30-fold) showed significantly different bound conformations between PKA and PKA-PKB chimera.
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'''STRUCTURE OF PKA-PKB CHIMERA COMPLEXED WITH (1-(9H-PURIN-6-YL)PIPERIDIN-4-YL)AMINE'''
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Identification of 4-(4-Aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration.,Caldwell JJ, Davies TG, Donald A, McHardy T, Rowlands MG, Aherne GW, Hunter LK, Taylor K, Ruddle R, Raynaud FI, Verdonk M, Workman P, Garrett MD, Collins I J Med Chem. 2008 Apr 10;51(7):2147-57. Epub 2008 Mar 18. PMID:18345609<ref>PMID:18345609</ref>
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==Overview==
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Fragment-based screening identified 7-azaindole as a protein kinase B inhibitor scaffold. Fragment elaboration using iterative crystallography of inhibitor-PKA-PKB chimera complexes efficiently guided improvements in the potency and selectivity of the compounds, resulting in the identification of nanomolar 6-(piperidin-1-yl)purine, 4-(piperidin-1-yl)-7-azaindole, and 4-(piperidin-1-yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative activity and showing pathway inhibition in cells. A divergence in the binding mode was seen between 4-aminomethylpiperidine and 4-aminopiperidine containing molecules. Selectivity for PKB vs PKA was observed with 4-aminopiperidine derivatives, and the most PKB-selective inhibitor (30-fold) showed significantly different bound conformations between PKA and PKA-PKB chimera.
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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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2VNY is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VNY OCA].
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</div>
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<div class="pdbe-citations 2vny" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Identification of 4-(4-Aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration., Caldwell JJ, Davies TG, Donald A, McHardy T, Rowlands MG, Aherne GW, Hunter LK, Taylor K, Ruddle R, Raynaud FI, Verdonk M, Workman P, Garrett MD, Collins I, J Med Chem. 2008 Apr 10;51(7):2147-57. Epub 2008 Mar 18. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18345609 18345609]
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*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bos taurus]]
[[Category: Bos taurus]]
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[[Category: Protein complex]]
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[[Category: Homo sapiens]]
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[[Category: CAMP-dependent protein kinase]]
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[[Category: Large Structures]]
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[[Category: Aherne, G W.]]
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[[Category: Aherne GW]]
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[[Category: Caldwell, J J.]]
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[[Category: Caldwell JJ]]
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[[Category: Collins, I.]]
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[[Category: Collins I]]
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[[Category: Davies, T G.]]
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[[Category: Davies TG]]
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[[Category: Donald, A.]]
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[[Category: Donald A]]
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[[Category: Garrett, M D.]]
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[[Category: Garrett MD]]
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[[Category: Hunter, L K.]]
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[[Category: Hunter LK]]
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[[Category: Mchardy, T.]]
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[[Category: McHardy T]]
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[[Category: Raynaud, F I.]]
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[[Category: Raynaud FI]]
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[[Category: Rowlands, M G.]]
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[[Category: Rowlands MG]]
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[[Category: Ruddle, R.]]
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[[Category: Ruddle R]]
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[[Category: Taylor, K.]]
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[[Category: Taylor K]]
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[[Category: Verdonk, M.]]
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[[Category: Verdonk M]]
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[[Category: Workman, P.]]
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[[Category: Workman P]]
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[[Category: Atp-binding]]
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[[Category: Camp]]
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[[Category: Cytoplasm]]
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[[Category: Kinase]]
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[[Category: Lipoprotein]]
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[[Category: Myristate]]
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[[Category: Nucleotide-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Protein kinase inhibitor]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:34:17 2008''
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Current revision

Structure of PKA-PKB chimera complexed with (1-(9H-Purin-6-yl) piperidin-4-yl)amine

PDB ID 2vny

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