3h9o

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{{STRUCTURE_3h9o| PDB=3h9o | SCENE= }}
 
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===Phosphoinositide-dependent protein kinase 1 (PDK-1) in complex with compound 9===
 
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{{ABSTRACT_PUBMED_19628388}}
 
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==About this Structure==
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==Phosphoinositide-dependent protein kinase 1 (PDK-1) in complex with compound 9==
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[[3h9o]] is a 1 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=3H9O OCA].
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<StructureSection load='3h9o' size='340' side='right'caption='[[3h9o]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3h9o]] is a 1 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=3H9O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3H9O FirstGlance]. <br>
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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]] 2.3&#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=9BD:2-(1H-IMIDAZOL-1-YL)-9-METHOXY-8-(2-METHOXYETHOXY)BENZO[C][2,7]NAPHTHYRIDIN-4-AMINE'>9BD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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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=3h9o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3h9o OCA], [https://pdbe.org/3h9o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3h9o RCSB], [https://www.ebi.ac.uk/pdbsum/3h9o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3h9o ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PDPK1_HUMAN PDPK1_HUMAN] Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages. Isoform 3 is catalytically inactive.<ref>PMID:9094314</ref> <ref>PMID:9768361</ref> <ref>PMID:9707564</ref> <ref>PMID:9445476</ref> <ref>PMID:10480933</ref> <ref>PMID:10995762</ref> <ref>PMID:12167717</ref> <ref>PMID:14585963</ref> <ref>PMID:14604990</ref> <ref>PMID:10226025</ref> <ref>PMID:16207722</ref> <ref>PMID:16251192</ref> <ref>PMID:17327236</ref> <ref>PMID:17371830</ref> <ref>PMID:18835241</ref>
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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/h9/3h9o_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=3h9o 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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A series of substituted benzo[c][2,7]-naphthyridines were prepared and showed good potency in inhibiting PDK-1. The synthesis and SAR of this series of compounds are presented as well as the X-ray crystal structure of one of these analogs in a complex with PDK-1.
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==Reference==
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Benzo[c][2,7]naphthyridines as inhibitors of PDK-1.,Kim KH, Wissner A, Floyd MB Jr, Fraser HL, Wang YD, Dushin RG, Hu Y, Olland A, Guo B, Arndt K Bioorg Med Chem Lett. 2009 Sep 1;19(17):5225-8. Epub 2009 Jul 8. PMID:19628388<ref>PMID:19628388</ref>
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<ref group="xtra">PMID:019628388</ref><references group="xtra"/>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 3h9o" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Pdk1 3D structures|Pdk1 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Large Structures]]
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[[Category: Olland, A M.]]
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[[Category: Olland AM]]
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[[Category: Atp-binding]]
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[[Category: Kinase]]
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[[Category: Membrane]]
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[[Category: Nucleotide-binding]]
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[[Category: Pdk-1]]
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[[Category: Phosphoprotein]]
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[[Category: Protein structure]]
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[[Category: Serine/threonine-protein kinase]]
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[[Category: Transferase]]
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[[Category: X-ray crysatllography]]
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Current revision

Phosphoinositide-dependent protein kinase 1 (PDK-1) in complex with compound 9

PDB ID 3h9o

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