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

Abstract

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

Oxytocin copper complex structure revealed by paramagnetic relaxation enhancement NMR analyses

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Acknowledgements

The authors would like to thank RECORD-IT project. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 664786; SY is the Benjamin H. Birstein Chair in Chemistry. IA is supported by a Hebrew University Center for Nanoscience and Nanotechnology Ph.D. scholarship.

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Correspondence to Deborah E. Shalev, Shlomo Yitzchaik or Mattan Hurevich.

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Alshanski, I., Shalev, D.E., Yitzchaik, S. et al. Determining the structure and binding mechanism of oxytocin-Cu2+ complex using paramagnetic relaxation enhancement NMR analysis. J Biol Inorg Chem 26, 809–815 (2021). https://doi.org/10.1007/s00775-021-01897-1

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Keywords

  • Nuclear magnetic resonance
  • Peptide
  • Copper complex
  • Oxytocin
  • Paramagnetic resonance enhancement