7rcu: Difference between revisions
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<table><tr><td colspan='2'>[[7rcu]] is a 24 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=7RCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCU FirstGlance]. <br> | <table><tr><td colspan='2'>[[7rcu]] is a 24 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=7RCU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RCU 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]] 2.69Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.69Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACM:ACETAMIDE'>ACM</scene>, <scene name='pdbligand=V7J:2-(2,5-dioxopyrrolidin-1-yl)acetamide'>V7J</scene></td></tr> | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=ACM:ACETAMIDE'>ACM</scene>, <scene name='pdbligand=D5M:2-DEOXYADENOSINE-5-MONOPHOSPHATE'>D5M</scene>, <scene name='pdbligand=V7J:2-(2,5-dioxopyrrolidin-1-yl)acetamide'>V7J</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=7rcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcu OCA], [https://pdbe.org/7rcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcu RCSB], [https://www.ebi.ac.uk/pdbsum/7rcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcu ProSAT]</span></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=7rcu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rcu OCA], [https://pdbe.org/7rcu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rcu RCSB], [https://www.ebi.ac.uk/pdbsum/7rcu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rcu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ | [https://www.uniprot.org/uniprot/MAX_HUMAN MAX_HUMAN] Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC-MAX complex is a transcriptional activator, whereas the MAD-MAX complex is a repressor. May repress transcription via the recruitment of a chromatin remodeling complex containing H3 'Lys-9' histone methyltransferase activity. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite unequivocal roles in disease, transcription factors (TFs) remain largely untapped as pharmacologic targets due to the challenges in targeting protein-protein and protein-DNA interactions. Here we report a chemical strategy to generate modular synthetic transcriptional repressors (STRs) derived from the bHLH domain of MAX. Our synthetic approach yields chemically stabilized tertiary domain mimetics that cooperatively bind the MYC/MAX consensus E-box motif with nanomolar affinity, exhibit specificity that is equivalent to or beyond that of full-length TFs and directly compete with MYC/MAX protein for DNA binding. A lead STR directly inhibits MYC binding in cells, downregulates MYC-dependent expression programs at the proteome level and inhibits MYC-dependent cell proliferation. Co-crystallization and structure determination of a STR:E-box DNA complex confirms retention of DNA recognition in a near identical manner as full-length bHLH TFs. We additionally demonstrate structure-blind design of STRs derived from alternative bHLH-TFs, confirming that STRs can be used to develop highly specific mimetics of TFs targeting other gene regulatory elements. | |||
Targeting MYC with modular synthetic transcriptional repressors derived from bHLH DNA-binding domains.,Speltz TE, Qiao Z, Swenson CS, Shangguan X, Coukos JS, Lee CW, Thomas DM, Santana J, Fanning SW, Greene GL, Moellering RE Nat Biotechnol. 2023 Apr;41(4):541-551. doi: 10.1038/s41587-022-01504-x. Epub , 2022 Oct 27. PMID:36302987<ref>PMID:36302987</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7rcu" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 19:42, 29 May 2024
Synthetic Max homodimer mimic in complex with DNA
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