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TitleStructural Insight Into a Human H Ferritin@Gold-Monocarbene Adduct: Aurophilicity Revealed in a Biological Context.
Journal, issue, pagesAngew Chem Int Ed Engl, Page e202503778, Year 2025
Publish dateApr 18, 2025
AuthorsLucrezia Cosottini / Andrea Giachetti / Annalisa Guerri / Ane Martinez-Castillo / Andrea Geri / Stefano Zineddu / Nicola G A Abrescia / Luigi Messori / Paola Turano / Antonio Rosato /
PubMed AbstractHuman 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 ...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 Å. 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.
External linksAngew Chem Int Ed Engl / PubMed:40249912
MethodsEM (single particle)
Resolution1.51 Å
Structure data

52339

9hq6

EMDB-52339, PDB-9hq6:
Structural insights in the HuHf@gold-monocarbene adduct: aurophilicity revealed in a biological context
Method: EM (single particle) / Resolution: 1.51 Å

Chemicals

ChemComp-BM0:
1-butyl-3-methyl-1H-imidazol-3-ium

ChemComp-AU:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
KeywordsMETAL BINDING PROTEIN / Iron / Gold / Metal transport / Metal storage / Anticancer drugs / Drug nanocarrier

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