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Updated: Jul 11, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Identification of the first peptide inhibitor of UBE2C enzymatic activity: insights from metadynamics-guided folding
Luciano Pirone1, Bianca Fiorillo2, Annarita Del Gatto1
1Institute of Biostructures and Bioimaging, Naples, Italy.
Abstract:
UBE2C (also known as UbcH10) is a ubiquitin-conjugating enzyme essential for mitotic progression and a potential therapeutic target in cancer. Here, we report a structure-based design and characterisation of peptides derived from a natural interacting partner (U1) aimed at modulating UBE2C activity. Biophysical and biochemical assays identified peptide 5 as a lead compound, capable of binding UBE2C with micromolar affinity and inhibiting the formation of the UBE2C-Ub thioester complex. Enhanced sampling molecular dynamics simulations revealed that peptide folding landscapes are correlated with activity, with active peptides sampling transient β-sheet conformations compatible with binding. To the best of our knowledge, this is the first report of a peptide inhibitor of UBE2C enzymatic activity.
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