7qpb

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<table><tr><td colspan='2'>[[7qpb]] is a 6 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=7QPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QPB FirstGlance]. <br>
<table><tr><td colspan='2'>[[7qpb]] is a 6 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=7QPB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7QPB 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]] 2.342&#8491;</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]] 2.342&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=GM1:AMINOMETHYLAMIDE'>GM1</scene>, <scene name='pdbligand=ZY9:6-(aminomethyl)pyridine-2-carboxylic+acid'>ZY9</scene></td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9JC:4-(aminomethyl)-8-azanyl-quinoline-2-carbaldehyde'>9JC</scene>, <scene name='pdbligand=9JV:8-azanyl-4-methoxy-quinoline-2-carboxylic+acid'>9JV</scene>, <scene name='pdbligand=CCS:CARBOXYMETHYLATED+CYSTEINE'>CCS</scene>, <scene name='pdbligand=GM1:AMINOMETHYLAMIDE'>GM1</scene>, <scene name='pdbligand=ZY9:6-(aminomethyl)pyridine-2-carboxylic+acid'>ZY9</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=7qpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpb OCA], [https://pdbe.org/7qpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpb RCSB], [https://www.ebi.ac.uk/pdbsum/7qpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpb 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=7qpb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7qpb OCA], [https://pdbe.org/7qpb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7qpb RCSB], [https://www.ebi.ac.uk/pdbsum/7qpb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7qpb ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Expanding the chemical diversity of peptide macrocycle libraries for display selection is desirable to improve their potential at binding biomolecular targets. We now have implemented a considerable expansion through a large aromatic helical foldamer inclusion. A helical aromatic foldamer was identified that undergoes flexizyme-mediated tRNA acylation and is capable of initiating ribosomal translation with yields sufficiently high to perform an mRNA display selection of macrocyclic foldamer-peptide hybrids. A hybrid macrocyle nanomolar binder to the C-lobe of the E6AP HECT domain was selected that showed a highly converged peptide sequence. A crystal structure and molecular dynamics simulations revealed that both the peptide and foldamer are helical in an intriguing reciprocal stapling fashion. The strong residue convergence could be rationalized based on their involvement in specific interactions with the target protein. The foldamer stabilizes the peptide helix through stapling and through contacts with key residues. These results altogether represent a significant extension of the chemical space amenable to display selection and highlight possible benefits of inserting an aromatic foldamer into a peptide macrocycle for the purpose of protein recognition.
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Expanding the chemical diversity of peptide macrocycle libraries for display selection is desirable to improve their potential to bind biomolecular targets. We now have implemented a considerable expansion through a large aromatic helical foldamer inclusion. A foldamer was first identified that undergoes flexizyme-mediated tRNA acylation and that is capable of initiating ribosomal translation with yields sufficiently high to perform an mRNA display selection of macrocyclic foldamer-peptide hybrids. A hybrid macrocyclic nanomolar binder to the C-lobe of the E6AP HECT domain was selected that showed a highly converged peptide sequence. A crystal structure and molecular dynamics simulations revealed that both the peptide and foldamer are helical in an intriguing reciprocal stapling fashion. The strong residue convergence could be rationalized based on their involvement in specific interactions with the target protein. The foldamer stabilizes the peptide helix through stapling and through contacts with key residues. These results altogether represent a significant extension of the chemical space amenable to display selection and highlight possible benefits of inserting an aromatic foldamer into a peptide macrocycle for the purpose of protein recognition.
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Display Selection of a Hybrid Foldamer-Peptide Macrocycle.,Dengler S, Howard RT, Morozov V, Tsiamantas C, Huang WE, Liu Z, Dobrzanski C, Pophristic V, Brameyer S, Douat C, Suga H, Huc I Angew Chem Int Ed Engl. 2023 Sep 14:e202308408. doi: 10.1002/anie.202308408. PMID:37707879<ref>PMID:37707879</ref>
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Display Selection of a Hybrid Foldamer-Peptide Macrocycle.,Dengler S, Howard RT, Morozov V, Tsiamantas C, Huang WE, Liu Z, Dobrzanski C, Pophristic V, Brameyer S, Douat C, Suga H, Huc I Angew Chem Int Ed Engl. 2023 Nov 13;62(46):e202308408. doi: , 10.1002/anie.202308408. Epub 2023 Oct 13. PMID:37707879<ref>PMID:37707879</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
<div class="pdbe-citations 7qpb" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 7qpb" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
== References ==
<references/>
<references/>

Current revision

Catalytic C-lobe of the HECT-type ubiquitin ligase E6AP in complex with a hybrid foldamer-peptide macrocycle

PDB ID 7qpb

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