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3ubw
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| - | [[Image:3ubw.jpg|left|200px]] | ||
| - | < | + | ==Complex of 14-3-3 isoform epsilon, a Mlf1 phosphopeptide and a small fragment hit from a FBDD screen== |
| - | + | <StructureSection load='3ubw' size='340' side='right'caption='[[3ubw]], [[Resolution|resolution]] 1.90Å' scene=''> | |
| - | + | == Structural highlights == | |
| - | + | <table><tr><td colspan='2'>[[3ubw]] is a 2 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=3UBW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UBW FirstGlance]. <br> | |
| - | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6SP:(3S)-PYRROLIDIN-3-OL'>6SP</scene>, <scene name='pdbligand=TBU:TERTIARY-BUTYL+ALCOHOL'>TBU</scene></td></tr> | |
| - | -- | + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr> |
| - | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ual|3ual]], [[2br9|2br9]]</div></td></tr> | |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YWHAE ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3ubw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ubw OCA], [https://pdbe.org/3ubw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ubw RCSB], [https://www.ebi.ac.uk/pdbsum/3ubw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ubw ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/1433E_HUMAN 1433E_HUMAN]] Distal 17p13.3 microdeletion syndrome;17p13.3 microduplication syndrome;Miller-Dieker syndrome. [[https://www.uniprot.org/uniprot/MLF1_HUMAN MLF1_HUMAN]] A chromosomal aberration involving MLF1 is a cause of myelodysplastic syndrome (MDS). Translocation t(3;5)(q25.1;q34) with NPM1/NPM. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/1433E_HUMAN 1433E_HUMAN]] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. [[https://www.uniprot.org/uniprot/MLF1_HUMAN MLF1_HUMAN]] Involved in lineage commitment of primary hemopoietic progenitors by restricting erythroid formation and enhancing myeloid formation. Interferes with erythropoietin-induced erythroid terminal differentiation by preventing cells from exiting the cell cycle through suppression of CDKN1B/p27Kip1 levels. Suppresses RFWD2/COP1 activity via CSN3 which activates p53 and induces cell cycle arrest. Binds DNA and affects the expression of a number of genes so may function as a transcription factor in the nucleus.<ref>PMID:15861129</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Myeloid leukaemia factor 1 (MLF1) binds to 14-3-3 adapter proteins by a sequence surrounding Ser34 with the functional consequences of this interaction largely unknown. We present here the high-resolution crystal structure of this binding motif [MLF1(29-42)pSer34] in complex with 14-3-3epsilon and analyse the interaction with isothermal titration calorimetry. Fragment-based ligand discovery employing crystals of the binary 14-3-3epsilon/MLF1(29-42)pSer34 complex was used to identify a molecule that binds to the interface rim of the two proteins, potentially representing the starting point for the development of a small molecule that stabilizes the MLF1/14-3-3 protein-protein interaction. Such a compound might be used as a chemical biology tool to further analyse the 14-3-3/MLF1 interaction without the use of genetic methods. Database Structural data are available in the Protein Data Bank under the accession number(s) 3UAL [14-3-3epsilon/MLF1(29-42)pSer34 complex] and 3UBW [14-3-3epsilon/MLF1(29-42)pSer34/3-pyrrolidinol complex] Structured digital abstract * 14-3-3 epsilon and MLF1 bind by x-ray crystallography (View interaction) * 14-3-3 epsilon and MLF1 bind by isothermal titration calorimetry (View Interaction: 1, 2). | ||
| - | + | Structural insights of the MLF1/14-3-3 interaction.,Molzan M, Weyand M, Rose R, Ottmann C FEBS J. 2011 Dec 8. doi: 10.1111/j.1742-4658.2011.08445.x. PMID:22151054<ref>PMID:22151054</ref> | |
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 3ubw" style="background-color:#fffaf0;"></div> | ||
| - | + | ==See Also== | |
| - | + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | |
| - | + | == References == | |
| - | + | <references/> | |
| - | + | __TOC__ | |
| - | + | </StructureSection> | |
| - | == | + | [[Category: Human]] |
| - | [[ | + | [[Category: Large Structures]] |
| - | + | [[Category: Molzan, M]] | |
| - | == | + | [[Category: Ottmann, C]] |
| - | < | + | [[Category: Rose, R]] |
| - | [[Category: | + | [[Category: Weyand, M]] |
| - | [[Category: Molzan, M | + | |
| - | [[Category: Ottmann, C | + | |
| - | [[Category: Rose, R | + | |
| - | [[Category: Weyand, M | + | |
[[Category: Adapter protein]] | [[Category: Adapter protein]] | ||
[[Category: Signaling protein]] | [[Category: Signaling protein]] | ||
[[Category: Signaling protein-protein binding complex]] | [[Category: Signaling protein-protein binding complex]] | ||
Current revision
Complex of 14-3-3 isoform epsilon, a Mlf1 phosphopeptide and a small fragment hit from a FBDD screen
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