7dno | pdb_00007dno
Characterization of Peptide Ligands Against WDR5 Isolated Using Phage Display Technique
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 PubMedWD40 is a ubiquitous domain presented in at least 361 human proteins and acts as scaffold to form protein complexes. Among them, WDR5 protein is an important mediator in several protein complexes to exert its functions in histone modification and chromatin remodeling. Therefore, it was considered as a promising epigenetic target involving in anti-cancer drug development. In view of the protein-protein interaction nature of WDR5, we initialized a campaign to discover new peptide-mimic inhibitors of WDR5. In current study, we utilized the phage display technique and screened with a disulfide-based cyclic peptide phage library. Five rounds of biopanning were performed and isolated clones were sequenced. By analyzing the sequences, total five peptides were synthesized for binding assay. The four peptides are shown to have the moderate binding affinity. Finally, the detailed binding interactions were revealed by solving a WDR5-peptide cocrystal structure. Phage-Display Based Discovery and Characterization of Peptide Ligands against WDR5.,Cao J, Fan T, Li Y, Du Z, Chen L, Wang Y, Wang X, Shen J, Huang X, Xiong B, Cao D Molecules. 2021 Feb 25;26(5):1225. doi: 10.3390/molecules26051225. PMID:33668971[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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