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The NAMI A – human ferritin system: a biophysical characterization†
Dalton Transactions ( IF 3.5 ) Pub Date : 2018-07-26 00:00:00 , DOI: 10.1039/c8dt00860d Silvia Ciambellotti 1, 2, 3, 4, 5 , Alessandro Pratesi 2, 3, 4, 5, 6 , Mirko Severi 2, 3, 4, 5 , Giarita Ferraro 4, 7, 8, 9, 10 , Enzo Alessio 4, 11, 12, 13 , Antonello Merlino 4, 7, 8, 9, 10 , Luigi Messori 2, 3, 4, 5, 6
Dalton Transactions ( IF 3.5 ) Pub Date : 2018-07-26 00:00:00 , DOI: 10.1039/c8dt00860d Silvia Ciambellotti 1, 2, 3, 4, 5 , Alessandro Pratesi 2, 3, 4, 5, 6 , Mirko Severi 2, 3, 4, 5 , Giarita Ferraro 4, 7, 8, 9, 10 , Enzo Alessio 4, 11, 12, 13 , Antonello Merlino 4, 7, 8, 9, 10 , Luigi Messori 2, 3, 4, 5, 6
Affiliation
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The reaction of the antimetastatic ruthenium(III) drug NAMI A with human H-chain ferritin (HuHf) was investigated through a variety of biophysical methods. We observed that the addition of HuHf to NAMI A solutions significantly increases the rate of spontaneous NAMI A hydrolysis suggesting the occurrence of a direct metallodrug–protein interaction. The resulting hydrolyzed Ru species binds the protein mostly forming a relatively tight 1 : 1 ruthenium/ferritin (subunit) adduct that was then separated and characterized. Notably, this adduct shows a characteristic CD spectrum in the visible region, which is diagnostic of the existence of at least one protein bound ruthenium center. The crystal structure of this NAMI A/HuHf adduct was subsequently solved at 1.58 Å resolution; clear evidence is given for the selective binding of a single Ru ion to His105 of each subunit with concomitant release of all other original Ru ligands in agreement with previous observations. We also noted that NAMI A produces a partial inhibition of HuHf ferroxidase activity. The implications of the above results are discussed.
中文翻译：
NAMI A –人类铁蛋白系统：生物物理特征†
抗静电钌的反应（Ⅲ）通过多种生物物理方法研究了含有人H链铁蛋白（HuHf）的药物NAMIA。我们观察到，将HuHf添加到NAMI A溶液中可显着提高自发NAMI A水解的速率，这表明金属金属-蛋白质直接相互作用的发生。所得的水解Ru物质与蛋白质结合，主要形成相对紧密的1：1钌/铁蛋白（亚基）加合物，然后对其进行分离和表征。明显地，该加合物在可见光区域显示出特征性的CD光谱，这诊断了至少一个蛋白质结合的钌中心的存在。随后以1.58Å的分辨率拆分了该NAMI A / HuHf加合物的晶体结构。有明确的证据表明，单个Ru离子与每个亚基的His105选择性结合，同时伴随着所有其他原始Ru配体的释放，这与以前的观察结果一致。我们还注意到，NAMI A产生对HuHf铁氧化酶活性的部分抑制。讨论了以上结果的含义。
更新日期：2018-07-26
中文翻译：
NAMI A –人类铁蛋白系统：生物物理特征†
抗静电钌的反应（Ⅲ）通过多种生物物理方法研究了含有人H链铁蛋白（HuHf）的药物NAMIA。我们观察到，将HuHf添加到NAMI A溶液中可显着提高自发NAMI A水解的速率，这表明金属金属-蛋白质直接相互作用的发生。所得的水解Ru物质与蛋白质结合，主要形成相对紧密的1：1钌/铁蛋白（亚基）加合物，然后对其进行分离和表征。明显地，该加合物在可见光区域显示出特征性的CD光谱，这诊断了至少一个蛋白质结合的钌中心的存在。随后以1.58Å的分辨率拆分了该NAMI A / HuHf加合物的晶体结构。有明确的证据表明，单个Ru离子与每个亚基的His105选择性结合，同时伴随着所有其他原始Ru配体的释放，这与以前的观察结果一致。我们还注意到，NAMI A产生对HuHf铁氧化酶活性的部分抑制。讨论了以上结果的含义。
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