3c4e

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{{Seed}}
 
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[[Image:3c4e.png|left|200px]]
 
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==Pim-1 Kinase Domain in Complex with 3-aminophenyl-7-azaindole==
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The line below this paragraph, containing "STRUCTURE_3c4e", creates the "Structure Box" on the page.
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<StructureSection load='3c4e' size='340' side='right'caption='[[3c4e]], [[Resolution|resolution]] 1.98&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'>[[3c4e]] is a 4 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=3C4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3C4E 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]] 1.98&#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=C4E:N-PHENYL-1H-PYRROLO[2,3-B]PYRIDIN-3-AMINE'>C4E</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene></td></tr>
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{{STRUCTURE_3c4e| PDB=3c4e | 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=3c4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3c4e OCA], [https://pdbe.org/3c4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3c4e RCSB], [https://www.ebi.ac.uk/pdbsum/3c4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3c4e ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PIM1_HUMAN PIM1_HUMAN] Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation and thus providing a selective advantage in tumorigenesis. Exerts its oncogenic activity through: the regulation of MYC transcriptional activity, the regulation of cell cycle progression and by phosphorylation and inhibition of proapoptotic proteins (BAD, MAP3K5, FOXO3). Phosphorylation of MYC leads to an increase of MYC protein stability and thereby an increase of transcriptional activity. The stabilization of MYC exerted by PIM1 might explain partly the strong synergism between these two oncogenes in tumorigenesis. Mediates survival signaling through phosphorylation of BAD, which induces release of the anti-apoptotic protein Bcl-X(L)/BCL2L1. Phosphorylation of MAP3K5, an other proapoptotic protein, by PIM1, significantly decreases MAP3K5 kinase activity and inhibits MAP3K5-mediated phosphorylation of JNK and JNK/p38MAPK subsequently reducing caspase-3 activation and cell apoptosis. Stimulates cell cycle progression at the G1-S and G2-M transitions by phosphorylation of CDC25A and CDC25C. Phosphorylation of CDKN1A, a regulator of cell cycle progression at G1, results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. Promote cell cycle progression and tumorigenesis by down-regulating expression of a regulator of cell cycle progression, CDKN1B, at both transcriptional and post-translational levels. Phosphorylation of CDKN1B,induces 14-3-3-proteins binding, nuclear export and proteasome-dependent degradation. May affect the structure or silencing of chromatin by phosphorylating HP1 gamma/CBX3. Acts also as a regulator of homing and migration of bone marrow cells involving functional interaction with the CXCL12-CXCR4 signaling axis.<ref>PMID:1825810</ref> <ref>PMID:10664448</ref> <ref>PMID:12431783</ref> <ref>PMID:15528381</ref> <ref>PMID:16356754</ref> <ref>PMID:18593906</ref> <ref>PMID:19749799</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/c4/3c4e_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3c4e ConSurf].
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<div style="clear:both"></div>
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===Pim-1 Kinase Domain in Complex with 3-aminophenyl-7-azaindole===
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==See Also==
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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*[[3D structures of pim-1|3D structures of pim-1]]
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== References ==
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<references/>
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(as it appears on PubMed at http://www.pubmed.gov), where 18287029 is the PubMed ID number.
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__TOC__
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</StructureSection>
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{{ABSTRACT_PUBMED_18287029}}
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==About this Structure==
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3C4E is a [[Single protein]] structure of 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=3C4E OCA].
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==Reference==
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Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity., Tsai J, Lee JT, Wang W, Zhang J, Cho H, Mamo S, Bremer R, Gillette S, Kong J, Haass NK, Sproesser K, Li L, Smalley KS, Fong D, Zhu YL, Marimuthu A, Nguyen H, Lam B, Liu J, Cheung I, Rice J, Suzuki Y, Luu C, Settachatgul C, Shellooe R, Cantwell J, Kim SH, Schlessinger J, Zhang KY, West BL, Powell B, Habets G, Zhang C, Ibrahim PN, Hirth P, Artis DR, Herlyn M, Bollag G, Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3041-6. Epub 2008 Feb 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18287029 18287029]
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[[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: Single protein]]
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[[Category: Wang W]]
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[[Category: Wang, W.]]
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[[Category: Zhang KYJ]]
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[[Category: Zhang, K Y.J.]]
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[[Category: Alternative initiation]]
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[[Category: Atp-binding]]
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[[Category: Cytoplasm]]
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[[Category: Manganese]]
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[[Category: Membrane]]
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[[Category: Metal-binding]]
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[[Category: Nucleotide-binding]]
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[[Category: Nucleus]]
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[[Category: Phosphoprotein]]
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[[Category: Pim-1]]
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[[Category: Proto-oncogene]]
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[[Category: Serine/threonine kinase]]
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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 Tue Jul 29 00:38:25 2008''
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Current revision

Pim-1 Kinase Domain in Complex with 3-aminophenyl-7-azaindole

PDB ID 3c4e

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