6QE9

The X-ray structure of the adduct formed in the reaction between bovine pancreatic ribonuclease and complex I, a pentacoordinate Pt(II) compound containing 2,9-dimethyl-1,10-phenanthroline, dimethylfumarate, methyl and iodine as ligands

Summary for 6QE9

• Entry DOI: 10.2210/pdb6qe9/pdb
• Descriptor: Ribonuclease pancreatic, SULFATE ION, pentacoordinate Pt(II) compound, ... (4 entities in total)
• Functional Keywords: five-coordinate pt complexes, anticancer platinum compounds, protein metal coordination, hydrolase
• Biological source: Bos taurus (cattle)
• Total number of polymer chains: 2
• Total formula weight: 28431.56

Authors

Merlino, A.,Ferraro, G. (deposition date: 2019-01-07, release date: 2019-02-27, Last modification date: 2024-11-06)

Primary citation

Ferraro, G.,Marzo, T.,Cucciolito, M.E.,Ruffo, F.,Messori, L.,Merlino, A.
Reaction with Proteins of a Five-Coordinate Platinum(II) Compound.
Int J Mol Sci, 20:-, 2019

PubMed Abstract: Stable five-coordinate Pt(II) complexes have been highlighted as a promising and original platform for the development of new cytotoxic drugs. Their interaction with proteins has been scarcely studied. Here, the reactivity of the five-coordinate Pt(II) compound [Pt(I)(Me) (dmphen)(olefin)] (Me = methyl, dmphen = 2,9-dimethyl-1,10-phenanthroline, olefin = dimethylfumarate) with the model proteins hen egg white lysozyme (HEWL) and bovine pancreatic ribonuclease (RNase A) has been investigated by X-ray crystallography and electrospray ionization mass spectrometry. The X-ray structures of the adducts of RNase A and HEWL with [Pt(I)(Me)(dmphen)(olefin)] are not of very high quality, but overall data indicate that, upon reaction with RNase A, the compound coordinates the side chain of His105 upon releasing the iodide ligand, but retains the pentacoordination. On the contrary, upon reaction with HEWL, the trigonal bi-pyramidal Pt geometry is lost, the iodide and the olefin ligands are released, and the metal center coordinates the side chain of His15 probably adopting a nearly square-planar geometry. This work underlines the importance of the combined use of crystallographic and mass spectrometry techniques to characterize, in detail, the protein⁻metallodrug recognition process. Our findings also suggest that five-coordinate Pt(II) complexes can act either retaining their uncommon structure or functioning as prodrugs, i.e., releasing square-planar platinum complexes as bioactive species.

PubMed: 30691130
DOI: 10.3390/ijms20030520

Experimental method

X-RAY DIFFRACTION (2.03 Å)