2vny: Difference between revisions
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==Structure of PKA-PKB chimera complexed with (1-(9H-Purin-6-yl) piperidin-4-yl)amine== | |||
<StructureSection load='2vny' size='340' side='right'caption='[[2vny]], [[Resolution|resolution]] 1.96Å' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.96Å</td></tr> | |||
<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> | |||
<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> | |||
</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/vn/2vny_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=2vny ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vny" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[CAMP-dependent protein kinase 3D structures|CAMP-dependent protein kinase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Bos taurus]] | [[Category: Bos taurus]] | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Aherne | [[Category: Aherne GW]] | ||
[[Category: Caldwell | [[Category: Caldwell JJ]] | ||
[[Category: Collins | [[Category: Collins I]] | ||
[[Category: Davies | [[Category: Davies TG]] | ||
[[Category: Donald | [[Category: Donald A]] | ||
[[Category: Garrett | [[Category: Garrett MD]] | ||
[[Category: Hunter | [[Category: Hunter LK]] | ||
[[Category: | [[Category: McHardy T]] | ||
[[Category: Raynaud | [[Category: Raynaud FI]] | ||
[[Category: Rowlands | [[Category: Rowlands MG]] | ||
[[Category: Ruddle | [[Category: Ruddle R]] | ||
[[Category: Taylor | [[Category: Taylor K]] | ||
[[Category: Verdonk | [[Category: Verdonk M]] | ||
[[Category: Workman | [[Category: Workman P]] | ||
Latest revision as of 01:27, 21 November 2024
Structure of PKA-PKB chimera complexed with (1-(9H-Purin-6-yl) piperidin-4-yl)amine
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