6iam: Difference between revisions
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==Modulating Protein-Protein Interactions with Visible Light Peptide Backbone Switches== | |||
<StructureSection load='6iam' size='340' side='right'caption='[[6iam]], [[Resolution|resolution]] 1.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6iam]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IAM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6IAM FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene></td></tr> | |||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=XY5:'>XY5</scene></td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">WDR5, BIG3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), SUMO1P1, SUMO5, UBL2, UBL6 ([http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6iam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iam OCA], [http://pdbe.org/6iam PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6iam RCSB], [http://www.ebi.ac.uk/pdbsum/6iam PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6iam ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/WDR5_HUMAN WDR5_HUMAN]] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.<ref>PMID:19556245</ref> <ref>PMID:19103755</ref> <ref>PMID:20018852</ref> <ref>PMID:16600877</ref> <ref>PMID:16829960</ref> [[http://www.uniprot.org/uniprot/SUMO5_HUMAN SUMO5_HUMAN]] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Regulates the life cycle of promyelocytic leukemia nuclear bodies (PML-NBs). PolySUMO1P1/SUMO5 conjugation on 'Lys-160' of PML facilitates recruitment of PML-NB components, which enlarges PML-NB. SUMO1P1/SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs.<ref>PMID:27211601</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Life relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators. | |||
Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches.,Albert L, Penalver A, Djokovic N, Werel L, Hoffarth M, Ruzic D, Xu J, Essen LO, Nikolic K, Dou Y, Vazquez O Chembiochem. 2019 Jun 3;20(11):1417-1429. doi: 10.1002/cbic.201800737. Epub 2019 , Apr 25. PMID:30675988<ref>PMID:30675988</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6iam" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Essen, L O]] | |||
[[Category: Werel, L]] | [[Category: Werel, L]] | ||
[[Category: | [[Category: Epigenetic transcriptional activation]] | ||
[[Category: Histone modification]] | |||
[[Category: Leukemia]] | |||
[[Category: Nsl complex]] | |||
[[Category: Osteoblasts differentiation]] | |||
[[Category: Transferase]] | |||
[[Category: Trimethylations at 'lys-4s']] | |||
Revision as of 09:13, 12 June 2019
Modulating Protein-Protein Interactions with Visible Light Peptide Backbone SwitchesModulating Protein-Protein Interactions with Visible Light Peptide Backbone Switches
Structural highlights
Function[WDR5_HUMAN] Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation.[1] [2] [3] [4] [5] [SUMO5_HUMAN] Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Regulates the life cycle of promyelocytic leukemia nuclear bodies (PML-NBs). PolySUMO1P1/SUMO5 conjugation on 'Lys-160' of PML facilitates recruitment of PML-NB components, which enlarges PML-NB. SUMO1P1/SUMO5 also increases polySUMO2/3 conjugation of PML, resulting in RNF4-mediated disruption of PML-NBs.[6] Publication Abstract from PubMedLife relies on a myriad of carefully orchestrated processes, in which proteins and their direct interplay ultimately determine cellular function and disease. Modulation of this complex crosstalk has recently attracted attention, even as a novel therapeutic strategy. Herein, we describe the synthesis and characterization of two visible-light-responsive peptide backbone photoswitches based on azobenzene derivatives, to exert optical control over protein-protein interactions (PPI). The novel peptidomimetics undergo fast and reversible isomerization with low photochemical fatigue under alternatively blue-/green-light irradiation cycles. Both bind in the nanomolar range to the protein of interest. Importantly, the best peptidomimetic displays a clear difference between isomers in its protein-binding capacity and, in turn, in its potential to inhibit enzymatic activity through PPI disruption. In addition, crystal structure determination, docking and molecular dynamics calculations allow a molecular interpretation and open up new avenues in the design and synthesis of future photoswitchable PPI modulators. Modulating Protein-Protein Interactions with Visible-Light-Responsive Peptide Backbone Photoswitches.,Albert L, Penalver A, Djokovic N, Werel L, Hoffarth M, Ruzic D, Xu J, Essen LO, Nikolic K, Dou Y, Vazquez O Chembiochem. 2019 Jun 3;20(11):1417-1429. doi: 10.1002/cbic.201800737. Epub 2019 , Apr 25. PMID:30675988[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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