Ubiquitin Conjugating Enzyme UbcH10, is a member of Ubiquitin Conjugation Enzymes (Ubc) family, involved in the regulation of cell cycle, and, when functionally altered, in cancer pathologies.[1,2] Here we present the de-novo design, the affinity assays and molecular dynamics studies of the binding mode of two peptide as candidate inhibitors of UbcH10-partner interaction. On the basis of the computational model of the quaternary complex between hUbA1, two ubiquitin molecules and the E2 enzyme, UbcH10, we have designed 3 families of 13-mer inhibitory peptides potentially able to impair UbcH10-partner interaction and UbcH10 activity. These peptides were synthetised biotinylated and subjected to affinity assays (ELISA) which allowed us to identify two potential leads, bearing to two different families, showing a sequence-dependent binding with micromolar affinity toward UbcH10. The binding mode of candidate leads was analysed by a computational study including peptide-protein docking and extensive molecular dynamics calculations.

From protein-protein interaction to E2 inhibitors leads: identification of peptide binding of UbcH10 / Morgillo, C. M.; Correale, S.; Federico, Antonella; DE PAOLA, Ivan; Forti, F.; Zaccaro, Laura; Monti, SIMONA MARIA; Pallante, Pierlorenzo; Galeone, Aldo; Luque, F. J.; Pedone, EMILIA MARIA; Catalanotti, Bruno; Fusco, Alfredo. - (2012). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei sistemi biologici tenutosi a Napoli nel 24/25 settembre 2012).

From protein-protein interaction to E2 inhibitors leads: identification of peptide binding of UbcH10

FEDERICO, ANTONELLA;DE PAOLA, IVAN;ZACCARO, LAURA;MONTI, SIMONA MARIA;PALLANTE, PIERLORENZO;GALEONE, ALDO;PEDONE, EMILIA MARIA;CATALANOTTI, BRUNO;FUSCO, ALFREDO
2012

Abstract

Ubiquitin Conjugating Enzyme UbcH10, is a member of Ubiquitin Conjugation Enzymes (Ubc) family, involved in the regulation of cell cycle, and, when functionally altered, in cancer pathologies.[1,2] Here we present the de-novo design, the affinity assays and molecular dynamics studies of the binding mode of two peptide as candidate inhibitors of UbcH10-partner interaction. On the basis of the computational model of the quaternary complex between hUbA1, two ubiquitin molecules and the E2 enzyme, UbcH10, we have designed 3 families of 13-mer inhibitory peptides potentially able to impair UbcH10-partner interaction and UbcH10 activity. These peptides were synthetised biotinylated and subjected to affinity assays (ELISA) which allowed us to identify two potential leads, bearing to two different families, showing a sequence-dependent binding with micromolar affinity toward UbcH10. The binding mode of candidate leads was analysed by a computational study including peptide-protein docking and extensive molecular dynamics calculations.
2012
From protein-protein interaction to E2 inhibitors leads: identification of peptide binding of UbcH10 / Morgillo, C. M.; Correale, S.; Federico, Antonella; DE PAOLA, Ivan; Forti, F.; Zaccaro, Laura; Monti, SIMONA MARIA; Pallante, Pierlorenzo; Galeone, Aldo; Luque, F. J.; Pedone, EMILIA MARIA; Catalanotti, Bruno; Fusco, Alfredo. - (2012). (Intervento presentato al convegno Convegno Nazionale della Divisione di Chimica dei sistemi biologici tenutosi a Napoli nel 24/25 settembre 2012).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/506175
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