Determining the structure and binding mechanism of oxytocin-Cu²⁺ complex using paramagnetic relaxation enhancement NMR analysis

Oxytocin is a neuropeptide that binds copper ions in nature. The structure of oxytocin in interaction with Cu²⁺ was determined here by NMR, showing which atoms of the peptide are involved in binding. Paramagnetic relaxation enhancement NMR analyses indicated a binding mechanism where the amino terminus was required for binding and subsequently Tyr2, Ile3 and Gln4 bound in that order. The aromatic ring of Tyr2 formed a π-cation interaction with Cu²⁺. Graphic abstract: [Figure not available: see fulltext.]