Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant.
Exploiting Electrode Nanoconfinement to Investigate the Catalytic Properties of Isocitrate Dehydrogenase (IDH1) and a Cancer-Associated Variant.
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DOI：
10.1021/acs.jpclett.1c01517
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发表时间：
2021-07-08
期刊：
影响因子：
--
通讯作者：
Armstrong FA
中科院分区：
文献类型：
--
作者：
Herold RA;Reinbold R;Megarity CF;Abboud MI;Schofield CJ;Armstrong FA
人异柠檬酸脱氢酶（IDH 1）及其癌症相关变体（IDH 1 R132 H）通过与快速NADP（H）再循环酶（铁氧还蛋白-NADP+还原酶）共限制在氧化铟锡电极内形成的纳米孔中而呈现电活性。与局部NADP（H）的有效偶联使得IDH活性能够被真实的激励、控制和监测，直接导致当R132 H变体存在时在生物环境中发生的癌代谢物2-羟基戊二酸积累的热力学氧化还原景观。该技术使时间分辨，在原位测量的抑制性药物的结合和解离的动力学。
Human isocitrate dehydrogenase (IDH1) and its cancer-associated variant (IDH1 R132H) are rendered electroactive through coconfinement with a rapid NADP(H) recycling enzyme (ferredoxin-NADP+ reductase) in nanopores formed within an indium tin oxide electrode. Efficient coupling to localized NADP(H) enables IDH activity to be energized, controlled, and monitored in real time, leading directly to a thermodynamic redox landscape for accumulation of the oncometabolite, 2-hydroxyglutarate, that would occur in biological environments when the R132H variant is present. The technique enables time-resolved, in situ measurements of the kinetics of binding and dissociation of inhibitory drugs.
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11.5
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作者：
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