4a7c

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[[Image:4a7c.png|left|200px]]
 
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==Crystal structure of PIM1 kinase with ETP46546==
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The line below this paragraph, containing "STRUCTURE_4a7c", creates the "Structure Box" on the page.
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<StructureSection load='4a7c' size='340' side='right'caption='[[4a7c]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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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'>[[4a7c]] 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=4A7C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A7C 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=E46:N-(PIPERIDIN-4-YLMETHYL)-3-[3-(TRIFLUOROMETHYLOXY)PHENYL]-[1,2,3]TRIAZOLO[4,5-B]PYRIDIN-5-AMINE'>E46</scene>, <scene name='pdbligand=IMD:IMIDAZOLE'>IMD</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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{{STRUCTURE_4a7c| PDB=4a7c | 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=4a7c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a7c OCA], [https://pdbe.org/4a7c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a7c RCSB], [https://www.ebi.ac.uk/pdbsum/4a7c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a7c 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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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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PIM kinases have become targets of interest due to their association with biochemical mechanisms affecting survival, proliferation and cytokine production. 1,2,3-Triazolo[4,5-b]pyridines were identified as PIM inhibitors applying a scaffold hopping approach. Initial exploration around this scaffold and X-ray crystallographic data are hereby described.
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===Crystal structure of PIM1 kinase with ETP46546===
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Hit to lead evaluation of 1,2,3-triazolo[4,5-b]pyridines as PIM kinase inhibitors.,Pastor J, Oyarzabal J, Saluste G, Alvarez RM, Rivero V, Ramos F, Cendon E, Blanco-Aparicio C, Ajenjo N, Cebria A, Albarran MI, Cebrian D, Corrionero A, Fominaya J, Montoya G, Mazzorana M Bioorg Med Chem Lett. 2012 Feb 15;22(4):1591-7. Epub 2012 Jan 5. PMID:22266039<ref>PMID:22266039</ref>
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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 4a7c" style="background-color:#fffaf0;"></div>
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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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(as it appears on PubMed at http://www.pubmed.gov), where 22266039 is the PubMed ID number.
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*[[3D structures of pim-1|3D structures of pim-1]]
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== References ==
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{{ABSTRACT_PUBMED_22266039}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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[[4a7c]] 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=4A7C OCA].
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==Reference==
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<ref group="xtra">PMID:022266039</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Mazzorana, M.]]
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[[Category: Large Structures]]
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[[Category: Montoya, G.]]
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[[Category: Mazzorana M]]
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[[Category: Inhibitor]]
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[[Category: Montoya G]]
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[[Category: Protein kinase]]
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[[Category: Transferase]]
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Current revision

Crystal structure of PIM1 kinase with ETP46546

PDB ID 4a7c

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