Cisplatin/Apo-Transferrin Adduct: X-ray Structure and Binding to the Transferrin Receptor 1.

Here, we report the X-ray structure of the adduct formed upon reaction of cisplatin, one of the most prescribed anticancer agents for the clinic treatment of solid tumors, with the apo-form of human serum transferrin (hTF). Two Pt binding sites were identified in both molecules of the adduct present in the crystal asymmetric unit: Pt binds close to the side chains of Met256 and Met499 at the N- and C-lobe, respectively. In the crystal structure, the cisplatin moiety bound to Met256 also interacts with Ser616 from a symmetry related molecule.

Deciphering the role of neutral diruthenium complexes in protein binding.

The charge of paddlewheel diruthenium complexes has a major role in defining their interaction with proteins: negatively charged complexes bind proteins non-covalently, while cationic complexes form adducts where the Ru core binds to Asp side chains at the equatorial sites, or to the main chain carbonyl groups or the side chains of His, Arg or Lys residues at the axial sites. Here we study the interactions of the neutral compound [Ru(D-p-FPhF)(OCCH)(OCO)]·3HO (D-p-FPhF = N,N'-bis(4-fluorophenyl)formamidinate), a very rare example of a paddlewheel diruthenium compound with three different equatorial ligands, with the model protein bovine pancreatic ribonuclease (RNase A) by means of UV-visible absorption spectroscopy, circular dichroism (CD), electrospray ionization mass spectrometry (ESI-MS) and X-ray crystallography. It is the first attempt to investigate the binding of a neutral diruthenium compound to a protein.

Cisplatin Binding to Human Serum Transferrin: A Crystallographic Study.

The molecular mechanism of how human serum transferrin (hTF) recognizes cisplatin at the atomic level is still unclear. Here, we report the molecular structure of the adduct formed upon the reaction of hTF with cisplatin. Pt binds the side chain of Met256 (at the N-lobe), without altering the protein overall conformation.