6iam: Difference between revisions
New page: '''Unreleased structure''' The entry 6iam is ON HOLD Authors: Werel, L., Essen, L.-O. Description: Modulating Protein-Protein Interactions with Visible Light Peptide Backbone Switches ... |
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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 [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://proteopedia.org/fgij/fg.htm?mol=6IAM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.51Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=XY5:2-[[(5~{Z})-8-azanyl-11,12-dihydrobenzo[c][1,2]benzodiazocin-3-yl]amino]ethanal'>XY5</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=6iam FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iam OCA], [https://pdbe.org/6iam PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iam RCSB], [https://www.ebi.ac.uk/pdbsum/6iam PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iam ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://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> | |||
<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> | ||
[[Category: | <div class="pdbe-citations 6iam" style="background-color:#fffaf0;"></div> | ||
[[Category: Essen | |||
==See Also== | |||
*[[WD-repeat protein 3D structures|WD-repeat protein 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Essen L-O]] | |||
[[Category: Werel L]] | |||
Latest revision as of 13:25, 15 November 2023
Modulating Protein-Protein Interactions with Visible Light Peptide Backbone SwitchesModulating Protein-Protein Interactions with Visible Light Peptide Backbone Switches
Structural highlights
FunctionWDR5_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] 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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