7c8e

Crystal Structure of 14-3-3 epsilon with 9J10 peptide

spinqualitylabelsall models 7c8e, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7c8e is a 4 chain structure with sequence from Homo sapiens and Streptomyces avermitilis MA-4680 = NBRC 14893. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.16Å Ligands: SEP, TRS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Genetic screening technologies to identify and validate macromolecular interactions (MMIs) essential for complex pathways remain an important unmet need for systems biology and therapeutics development. Here, we use a library of peptides from diverse prokaryal genomes to screen MMIs promoting the nuclear relocalization of Forkhead Box O3 (FOXO3a), a tumor suppressor more frequently inactivated by post-translational modification than mutation. A hit peptide engages the 14-3-3 family of signal regulators through a phosphorylation-dependent interaction, modulates FOXO3a-mediated transcription, and suppresses cancer cell growth. In a crystal structure, the hit peptide occupies the phosphopeptide-binding groove of 14-3-3epsilon in a conformation distinct from its natural peptide substrates. A biophysical screen identifies drug-like small molecules that displace the hit peptide from 14-3-3epsilon, providing starting points for structure-guided development. Our findings exemplify "protein interference," an approach using evolutionarily diverse, natural peptides to rapidly identify, validate, and develop chemical probes against MMIs essential for complex cellular phenotypes. Target identification for small-molecule discovery in the FOXO3a tumor-suppressor pathway using a biodiverse peptide library.,Emery A, Hardwick BS, Crooks AT, Milech N, Watt PM, Mithra C, Kumar V, Giridharan S, Sadasivam G, Mathivanan S, Sudhakar S, Bairy S, Bharatham K, Hurakadli MA, Prasad TK, Kamariah N, Muellner M, Coelho M, Torrance CJ, McKenzie GJ, Venkitaraman AR Cell Chem Biol. 2021 Nov 18;28(11):1602-1615.e9. doi: , 10.1016/j.chembiol.2021.05.009. Epub 2021 Jun 9. PMID:34111400 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 14-3-3 protein 3D structures

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