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Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase

Marcello, Tortorici, Borrello, Maria Teresa and Tardugno, Maria (2013) Protein Recognition by Short Peptide Reversible Inhibitors of the Chromatin-Modifying LSD1/CoREST Lysine Demethylase. ACS CHEMICAL BIOLOGY, 8 (8). pp. 1677-1682. ISSN 1554-8929

Item Type: Article


The combinatorial assembly of protein complexes is at the heart of chromatin biology. Lysine demethylaseLSD1(KDM1A)/CoREST beautifully exemplifies this concept. The active site of the enzyme tightly associates to the N-terminaldomain of transcription factors of the SNAIL1 family, which therefore can competitively inhibit the binding of the N-terminal tailof the histone substrate. Our enzymatic, crystallographic, spectroscopic, and computational studies reveal that LSD1/CoRESTcan bind to a hexapeptide derived from the SNAIL sequence through recognition of a positively chargedĪ±-helical turn that formsupon binding to the enzyme. Variations in sequence and length of this six amino acid ligand modulate affinities enabling the samebinding site to differentially interact with proteins that exert distinct biological functions. The discovered short peptide inhibitorsexhibit antiproliferative activities and lay the foundation for the development of peptidomimetic small molecule inhibitors ofLSD1

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Depositing User: Teresa Borrello


Item ID: 17417
Identification Number:
ISSN: 1554-8929
Official URL:

Users with ORCIDS

ORCID for Maria Teresa Borrello: ORCID iD

Catalogue record

Date Deposited: 11 Mar 2024 12:53
Last Modified: 11 Mar 2024 13:00


Author: Maria Teresa Borrello ORCID iD
Author: Tortorici Marcello
Author: Maria Tardugno

University Divisions

Faculty of Health Sciences and Wellbeing > School of Pharmacy and Pharmaceutical Sciences


Sciences > Chemistry
Sciences > Pharmacy and Pharmacology

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