Inhibition of the purified 20S proteasome by non-heme iron complexes.
Inhibition of the purified 20S proteasome by non-heme iron complexes.
复制标题
非血红素铁复合物对纯化 20S 蛋白酶体的抑制。
DOI：
10.1039/c2mt00131d
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Kodanko,JeremyJ
中科院分区：
文献类型：
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作者：
Prakash,Jai;Schmitt,SaraM;Dou,QPing;Kodanko,JeremyJ
Polypyridyl pentadentate ligands N4Py (1) and Bn-TPEN (2), along with their respective iron complexes, have been investigated for their ability to inhibit the purified 20S proteasome. Results demonstrated that the iron complexes of both ligands are potent inhibitors of the 20S proteasome (IC50= 9.2 μM for [FeII(OH2)(N4Py)]2+(3) and 4.0 μM for [FeII(OH2)(Bn-TPEN)]2+(4)). Control experiments showed that ligand1or FeIIalone showed no inhibition, whereas2was moderately active (IC50= 96 μM), suggesting that iron, when bound to these ligands, plays a key role in proteasome inhibition. Results from time-dependent inactivation studies suggest different modes of action for the iron complexes. Time-dependent decay of proteasome activity was observed upon incubation in the presence of4, which accelerated in the presence of DTT, suggesting reductive activation of O2and oxidation of the 20S proteasome as a mode of action. In contrast, loss of 20S proteasome activity was not observed with3over time, suggesting inhibition through direct binding of the iron complex to the enzyme. Inhibition of the 20S proteasome by4was not blocked by reactive oxygen species scavengers, consistent with a unique oxidant being responsible for the time-dependent inhibition observed.
