5jm4
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==Crystal structure of 14-3-3zeta in complex with a cyclic peptide involving an adamantyl and a dicarboxy side chain== | ==Crystal structure of 14-3-3zeta in complex with a cyclic peptide involving an adamantyl and a dicarboxy side chain== | ||
| - | <StructureSection load='5jm4' size='340' side='right' caption='[[5jm4]], [[Resolution|resolution]] 2.34Å' scene=''> | + | <StructureSection load='5jm4' size='340' side='right'caption='[[5jm4]], [[Resolution|resolution]] 2.34Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5jm4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JM4 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5jm4]] is a 4 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=5JM4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JM4 FirstGlance]. <br> |
| - | </td></tr><tr id=' | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.34Å</td></tr> |
| - | <tr id=' | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6L9:[(2S)-2,3-DIAMINO-3-OXOPROPYL]PROPANEDIOIC+ACID'>6L9</scene>, <scene name='pdbligand=A1G:(2S)-AMINO[(3R,5R,7R)-TRICYCLO[3.3.1.1~3,7~]DECAN-1-YL]ACETIC+ACID'>A1G</scene>, <scene name='pdbligand=BEZ:BENZOIC+ACID'>BEZ</scene>, <scene name='pdbligand=MKD:(2S)-2-AMINO-2-METHYLOCTANOIC+ACID'>MKD</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=5jm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jm4 OCA], [https://pdbe.org/5jm4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jm4 RCSB], [https://www.ebi.ac.uk/pdbsum/5jm4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jm4 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/1433Z_HUMAN 1433Z_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.<ref>PMID:9360956</ref> <ref>PMID:14578935</ref> <ref>PMID:15071501</ref> <ref>PMID:15644438</ref> <ref>PMID:16376338</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Macrocyclic peptides can interfere with challenging biomolecular targets including protein-protein interactions. Whereas there are various approaches that facilitate the identification of peptide-derived ligands, their evolution into higher affinity binders remains a major hurdle. We report a virtual screen based on molecular docking that allows the affinity maturation of macrocyclic peptides taking non-natural amino acids into consideration. These macrocycles bear large and flexible substituents that usually complicate the use of docking approaches. A virtual library containing more than 1400 structures was screened against the target focusing on docking poses with the core structure resembling a known bioactive conformation. Based on this screen, a macrocyclic peptide 22 involving two non-natural amino acids was evolved showing increased target affinity and biological activity. Predicted binding modes were verified by X-ray crystallography. The presented workflow allows the screening of large macrocyclic peptides with diverse modifications thereby expanding the accessible chemical space and reducing synthetic efforts. | ||
| + | |||
| + | Structure-Based Design of Non-natural Macrocyclic Peptides That Inhibit Protein-Protein Interactions.,Kruger DM, Glas A, Bier D, Pospiech N, Wallraven K, Dietrich L, Ottmann C, Koch O, Hennig S, Grossmann TN J Med Chem. 2017 Nov 9;60(21):8982-8988. doi: 10.1021/acs.jmedchem.7b01221. Epub , 2017 Oct 27. PMID:29028171<ref>PMID:29028171</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5jm4" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Synthetic construct]] |
| - | [[Category: | + | [[Category: Bier D]] |
| - | + | [[Category: Glas A]] | |
| - | [[Category: | + | [[Category: Grossmann T]] |
| - | [[Category: | + | [[Category: Hennig S]] |
| - | [[Category: | + | [[Category: Krueger D]] |
| - | [[Category: | + | [[Category: Ottmann C]] |
| - | [[Category: | + | [[Category: Wallraven K]] |
| - | [[Category: | + | |
Current revision
Crystal structure of 14-3-3zeta in complex with a cyclic peptide involving an adamantyl and a dicarboxy side chain
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