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Publication Abstract from PubMed

Human H ferritin (HuHf) has excellent potential as a nanocarrier for the selective delivery of anticancer metal-based drugs to tumor cells. Here, we addressed the interaction of the gold monocarbene compound Au(NHC)Cl with HuHf by electrospray ionization-mass spectrometry (ESI-MS) measurements, which provide the metalation state of the protein subunits and demonstrate the involvement of protein cysteines in gold binding. The adduct between Au(NHC)Cl and HuHf was studied by cryo-EM measurements, resulting in a high-resolution 3D density map at 1.51 A. The cryo-EM structure shows a novel tetranuclear gold(I) cluster, located in a surface pocket of each subunit where it is bound to Cys90 and Cys102. The short inter-metal distances are diagnostic of the occurrence of aurophilic interactions. The present work demonstrates the usefulness of cryo-EM to investigate the interactions between metal-based drugs and their protein targets/carriers, also leveraging the strong signal of transition metal ions.

Structural Insight Into a Human H Ferritin@Gold-Monocarbene Adduct: Aurophilicity Revealed in a Biological Context.,Cosottini L, Giachetti A, Guerri A, Martinez-Castillo A, Geri A, Zineddu S, Abrescia NGA, Messori L, Turano P, Rosato A Angew Chem Int Ed Engl. 2025 Apr 18:e202503778. doi: 10.1002/anie.202503778. PMID:40249912^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.