6QEA

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

6QEA の概要

• エントリーDOI: 10.2210/pdb6qea/pdb
• 分子名称: Lysozyme C, NITRATE ION, pentacoordinate Pt(II) compound, ... (5 entities in total)
• 機能のキーワード: five-coordinate pt complexes, anticancer platinum compounds, protein metal coordination, lyase
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15178.74

構造登録者

Merlino, A.,Ferraro, G. (登録日: 2019-01-07, 公開日: 2019-03-27, 最終更新日: 2024-11-20)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.96 Å)