6WRM

The interaction of chlorido(1,5-cyclooctadiene)([4-(2-((tert-butoxycarbonyl)amino)-3-methoxy-3-oxopropyl)-1,3-dimethyl-1H-imidazol-3-ide])rhodium(I) with HEWL after 1 month

6WRM の概要

• エントリーDOI: 10.2210/pdb6wrm/pdb
• 分子名称: Lysozyme, SODIUM ION, CHLORIDE ION, ... (6 entities in total)
• 機能のキーワード: metal-based, anticancer, rhodium, nhc, carbene, hewl, hen egg white lysozyme, lysozyme, metallodrug, imidazole, hydrolase
• 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: 14928.22

構造登録者

Sullivan, M.P.,John, M.,Hartinger, C.G.,Goldstone, D.C. (登録日: 2020-04-29, 公開日: 2020-12-16, 最終更新日: 2024-11-13)

主引用文献

Daubit, I.M.,Sullivan, M.P.,John, M.,Goldstone, D.C.,Hartinger, C.G.,Metzler-Nolte, N.
A Combined Spectroscopic and Protein Crystallography Study Reveals Protein Interactions of Rh I (NHC) Complexes at the Molecular Level.
Inorg.Chem., 59:17191-17199, 2020

PubMed Abstract: While most Rh-N-heterocyclic carbene (NHC) complexes currently investigated in anticancer research contain a Rh(III) metal center, an increasing amount of research is focusing on the cytotoxic activity and mode of action of square-planar [RhCl(COD)(NHC)] (where COD = 1,5-cyclooctadiene) which contains a Rh(I) center. The enzyme thioredoxin reductase (TrxR) and the protein albumin have been proposed as potential targets, but the molecular processes taking place upon protein interaction remain elusive. Herein, we report the preparation of peptide-conjugated and its nonconjugated parent [RhCl(COD)(NHC)] complexes, an in-depth investigation of both their stability in solution, and a crystallographic study of protein interaction. The organorhodium compounds showed a rapid loss of the COD ligand and slow loss of the NHC ligand in aqueous solution. These ligand exchange reactions were reflected in studies on the interaction with hen egg white lysozyme (HEWL) as a model protein in single-crystal X-ray crystallographic investigations. Upon treatment of HEWL with an amino acid functionalized [RhCl(COD)(NHC)] complex, two distinct rhodium adducts were found initially after 7 d of incubation at His15 and after 4 weeks also at Lys33. In both cases, the COD and chlorido ligands had been substituted with aqua and/or hydroxido ligands. While the histidine (His) adduct also indicated a loss of the NHC ligand, the lysine (Lys) adduct retained the NHC core derived from the amino acid l-histidine. In either case, an octahedral coordination environment of the metal center indicates oxidation to Rh(III). This investigation gives the first insight on the interaction of Rh(I)(NHC) complexes and proteins at the molecular level.

PubMed: 33180473
DOI: 10.1021/acs.inorgchem.0c02438

実験手法

X-RAY DIFFRACTION (1.55 Å)