Femtosecond dynamics of a drug–protein complex: Daunomycin with Apo riboflavin-binding protein
Femtosecond dynamics of a drug–protein complex: Daunomycin with Apo riboflavin-binding protein
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药物-蛋白质复合物的飞秒动力学：道诺霉素与 Apo 核黄素结合蛋白
DOI：
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发表时间：
2001
影响因子：
11.1
通讯作者：
A. Zewail
中科院分区：
文献类型：
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作者：
D. Zhong;S. Pal;C. Wan;A. Zewail
在这篇文章中，我们报道了柔红霉素与脱脂核黄素结合蛋白药物-蛋白质复合体的初级动力学研究。利用飞秒分辨，我们观察到柔红霉素与蛋白质色氨酸的芳香族氨基酸残基(S)之间的超快电荷分离。从色氨酸(S)到柔红霉素的电子转移有两个反应时间，根据局部络合物结构的不同，分别为1ps和6ps。在氧化还原循环中，阴离子柔红霉素自由基的形成是引发一系列化学反应的关键。随后的反应之一是被还原的柔红霉素将氧气还原为活性超氧化物。这一催化过程发生在10ps内。在没有氧气的情况下，电荷复合所需的时间要长得多，超过100ps。这些结果，以及在DNA和核苷酸中的类似发现，阐明了通过光激活超快产生还原的柔红霉素自由基是观察到的药物细胞毒性光增强几个数量级的主要步骤。我们还研究了不同离子强度和变性剂浓度下蛋白质构象对动力学的依赖关系。我们观察到在变性剂浓度为2M时，从三级结构到展开状态的急剧转变。
In this contribution, we report studies of the primary dynamics of the drug–protein complexes of daunomycin with apo riboflavin-binding protein. With femtosecond resolution, we observed the ultrafast charge separation between daunomycin and aromatic amino acid residues of the protein, tryptophan(s). Electron transfer occurs from tryptophan(s) to daunomycin with two reaction times, 1 ps and 6 ps, depending on the local complex structure. The formation of anionic daunomycin radical is crucial for triggering a series of chemical reactions in redox cycling. One of the subsequent reactions is the reduction of dioxygen to form active superoxide by the reduced daunomycin. This catalytic process was found to occur within 10 ps. In the absence of dioxygen, charge recombination takes a much longer time, more than 100 ps. These results, along with similar findings in DNA and nucleotides, elucidate that the ultrafast generation of reduced daunomycin radicals by photoactivation is a primary step for the observed photoenhancement of drug cytotoxicity by several orders of magnitude. We also studied the dependence of the dynamics on protein conformations at different ionic strengths and denaturant concentrations. We observe a sharp transition from the tertiary structure to the unfolding state at 2 M of denaturant concentration.
影响因子：
7.3
作者：
D. Taatjes;G. Gaudiano;K. Resing;T. Koch
通讯作者：
D. Taatjes;G. Gaudiano;K. Resing;T. Koch
影响因子：
2.9
作者：
CHAIRES, JB;DATTAGUPTA, N;CROTHERS, DM
通讯作者：
CROTHERS, DM
影响因子：
2.9
作者：
CHAIRES, JB;DATTAGUPTA, N;CROTHERS, DM
通讯作者：
CROTHERS, DM