3cy3: Difference between revisions
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< | ==Crystal structure of human proto-oncogene serine threonine kinase (PIM1) in complex with a consensus peptide and the JNK inhibitor V== | ||
<StructureSection load='3cy3' size='340' side='right'caption='[[3cy3]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3cy3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CY3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CY3 FirstGlance]. <br> | |||
or | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=JN5:(2S)-1,3-BENZOTHIAZOL-2-YL{2-[(2-PYRIDIN-3-YLETHYL)AMINO]PYRIMIDIN-4-YL}ETHANENITRILE'>JN5</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=3cy3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cy3 OCA], [https://pdbe.org/3cy3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cy3 RCSB], [https://www.ebi.ac.uk/pdbsum/3cy3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cy3 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/cy/3cy3_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</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/main_output.php?pdb_ID=3cy3 ConSurf]. | |||
<div style="clear:both"></div> | |||
=== | ==See Also== | ||
*[[Serine/threonine protein kinase 3D structures|Serine/threonine protein kinase 3D structures]] | |||
*[[3D structures of pim-1|3D structures of pim-1]] | |||
== | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Synthetic construct]] | ||
[[Category: Arrowsmith | [[Category: Arrowsmith CH]] | ||
[[Category: Bountra | [[Category: Bountra C]] | ||
[[Category: Bullock | [[Category: Bullock A]] | ||
[[Category: Edwards AM]] | |||
[[Category: Edwards | [[Category: Fedorov O]] | ||
[[Category: Fedorov | [[Category: Filippakopoulos P]] | ||
[[Category: Filippakopoulos | [[Category: Knapp S]] | ||
[[Category: Knapp | [[Category: Pike ACW]] | ||
[[Category: Pike | [[Category: Von Delft F]] | ||
[[Category: | |||