3bgp

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[[Image:3bgp.gif|left|200px]]
 
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==Human Pim-1 complexed with a benzoisoxazole inhibitor VX1==
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The line below this paragraph, containing "STRUCTURE_3bgp", creates the "Structure Box" on the page.
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<StructureSection load='3bgp' size='340' side='right'caption='[[3bgp]], [[Resolution|resolution]] 2.80&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'>[[3bgp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BGP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BGP FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VX1:4-[3-(4-CHLOROPHENYL)-2,1-BENZISOXAZOL-5-YL]PYRIMIDIN-2-AMINE'>VX1</scene></td></tr>
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<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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{{STRUCTURE_3bgp| PDB=3bgp | SCENE= }}
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bgq|3bgq]], [[3bgz|3bgz]]</div></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIM1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span></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=3bgp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bgp OCA], [https://pdbe.org/3bgp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bgp RCSB], [https://www.ebi.ac.uk/pdbsum/3bgp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bgp 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/bg/3bgp_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=3bgp 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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To supplement the hits from a high throughput screen, docking was performed against Pim-1 kinase. Glide docking was augmented with a filter to require traditional or aromatic CH..O hydrogen bonds to the kinase hinge. Four diverse actives, of 96 molecules assayed, had K(i) values between 0.091 and 4.5 microM. This gives a 14-fold enrichment over the earlier HTS run, and the two crystal structures solved confirmed the binding modes predicted by docking.
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'''Human Pim-1 complexed with a benzoisoxazole inhibitor VX1'''
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Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase.,Pierce AC, Jacobs M, Stuver-Moody C J Med Chem. 2008 Mar 27;51(6):1972-5. Epub 2008 Feb 22. PMID:18290603<ref>PMID:18290603</ref>
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==Overview==
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To supplement the hits from a high throughput screen, docking was performed against Pim-1 kinase. Glide docking was augmented with a filter to require traditional or aromatic CH..O hydrogen bonds to the kinase hinge. Four diverse actives, of 96 molecules assayed, had K(i) values between 0.091 and 4.5 microM. This gives a 14-fold enrichment over the earlier HTS run, and the two crystal structures solved confirmed the binding modes predicted by docking.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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3BGP 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=3BGP OCA].
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</div>
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<div class="pdbe-citations 3bgp" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Docking study yields four novel inhibitors of the protooncogene Pim-1 kinase., Pierce AC, Jacobs M, Stuver-Moody C, J Med Chem. 2008 Mar 27;51(6):1972-5. Epub 2008 Feb 22. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18290603 18290603]
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*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]]
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[[Category: Homo sapiens]]
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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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__TOC__
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</StructureSection>
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[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]
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[[Category: Single protein]]
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[[Category: Jacobs, M D]]
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[[Category: Jacobs, M D.]]
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[[Category: Alternative initiation]]
[[Category: Alternative initiation]]
[[Category: Atp-binding]]
[[Category: Atp-binding]]
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[[Category: Serine/threonine-protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Apr 30 13:38:41 2008''
 

Current revision

Human Pim-1 complexed with a benzoisoxazole inhibitor VX1

PDB ID 3bgp

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