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Organometallic ruthenium anticancer complexes inhibit human peroxiredoxin I activity by binding to and inducing oxidation of its catalytic cysteine residue.
- Source :
-
Metallomics : integrated biometal science [Metallomics] 2019 Mar 20; Vol. 11 (3), pp. 546-555. - Publication Year :
- 2019
-
Abstract
- Peroxiredoxins (Prxs) are a family of ubiquitous antioxidant proteins and the inhibition of Prxs would elevate the reactive oxygen species level so as to induce cancer cell death. The interactions of organometallic ruthenium arene anticancer complexes with proteins play important roles in their mechanisms of action. Herein, we demonstrate that Ru complexes [(η6-arene)Ru(en)Cl]+ (en = ethylenediamine, arene = p-cymene (1), biphenyl (2) and 9,10-dihydrophenanthrene (3)) can inhibit the enzymatic activity of human peroxiredoxin I (Prx-I) in an order of 1 > 3 > 2. Mass spectrometric (MS) analysis revealed that 1-3 coordinated to the catalytic site Cys173 of Prx-I, and partially induced the oxidation of the thiolate to sulfenate. Quantitative MS analysis demonstrated that the higher level of the ruthenation of Cys173 is correlated with the higher inhibitory potency of the Ru complexes against Prx-I, suggesting their binding to Cys173 accounts for their inhibition towards Prx-I.
- Subjects :
- Antineoplastic Agents chemistry
Antineoplastic Agents metabolism
Binding Sites
Cysteine chemistry
Models, Molecular
Organometallic Compounds chemistry
Organometallic Compounds metabolism
Oxidation-Reduction drug effects
Ruthenium chemistry
Ruthenium metabolism
Antineoplastic Agents pharmacology
Cysteine metabolism
Organometallic Compounds pharmacology
Peroxiredoxins antagonists & inhibitors
Peroxiredoxins chemistry
Peroxiredoxins metabolism
Ruthenium pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1756-591X
- Volume :
- 11
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Metallomics : integrated biometal science
- Publication Type :
- Academic Journal
- Accession number :
- 30693924
- Full Text :
- https://doi.org/10.1039/c8mt00352a