2x39: Difference between revisions

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==STRUCTURE OF 4-AMINO-N-(4-CHLOROBENZYL)-1-(7H-PYRROLO(2,3-D) PYRIMIDIN-4-YL)PIPERIDINE-4-CARBOXAMIDE BOUND TO PKB==
 
<StructureSection load='2x39' size='340' side='right' caption='[[2x39]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
==Structure of 4-Amino-N-(4-chlorobenzyl)-1-(7H-pyrrolo(2,3-d)pyrimidin- 4-yl)piperidine-4-carboxamide bound to PKB==
<StructureSection load='2x39' size='340' side='right'caption='[[2x39]], [[Resolution|resolution]] 1.93&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2X39 FirstGlance]. <br>
<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>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
</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='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2uw9|2uw9]], [[1o6k|1o6k]], [[1gng|1gng]], [[1h8f|1h8f]], [[1q3w|1q3w]], [[1i09|1i09]], [[1o9u|1o9u]], [[2x37|2x37]], [[2jdr|2jdr]], [[1o6l|1o6l]], [[1j1b|1j1b]], [[1r0e|1r0e]], [[1q41|1q41]], [[1q3d|1q3d]], [[2jld|2jld]], [[1q5k|1q5k]], [[2jdo|2jdo]], [[1pyx|1pyx]], [[1q4l|1q4l]], [[1j1c|1j1c]], [[1uv5|1uv5]]</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=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>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2x39 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x39 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2x39 RCSB], [http://www.ebi.ac.uk/pdbsum/2x39 PDBsum]</span></td></tr>
</table>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/GSK3B_HUMAN GSK3B_HUMAN]] Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation.<ref>PMID:1846781</ref> <ref>PMID:8397507</ref> <ref>PMID:9072970</ref> <ref>PMID:9819408</ref> <ref>PMID:11430833</ref> <ref>PMID:14690523</ref> <ref>PMID:15448698</ref> <ref>PMID:18348280</ref> <ref>PMID:20932480</ref> <ref>PMID:20937854</ref> <ref>PMID:22514281</ref> <ref>PMID:12554650</ref> 
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/x3/2x39_consurf.spt"</scriptWhenChecked>
     <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/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
</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="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 2x39" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Serine/threonine protein kinase|Serine/threonine protein kinase]]
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
== References ==
== References ==
<references/>
<references/>
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[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]]
Retrieved from "https://proteopedia.org/2x39"