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Kinetic studies on iron release from transferrins.

机译:从转铁蛋白中释放铁的动力学研究。

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摘要

The transferrin superfamily includes serum transferrin in vertebrates and the ferric binding protein (FBP) in some Gram-negative pathogens. Both of them can reversibly bind iron and play a significant role in iron metabolism.;Extensive kinetic studies have been reported on iron release from serum transferrin, but a detailed iron release mechanism has not yet been established. Our studies have focused on the effect of pH on two proposed pathways for iron release from transferrin by several chelating agents. Additional information on the specific protonation events during iron release has been obtained from studies in which site-directed mutagenesis has been used to eliminate lysine residues that have been proposed to function as a pH-sensitive "trigger" for conformational changes in the protein that regulate the rate of iron release.;Kinetic studies on iron release from FBP by a variety of ligands have been conducted and several short-lived intermediates have been detected spectroscopically. A general mechanism of iron release from this protein is proposed. Most ligands remove iron from the protein very quickly, but one ligand, nitrilotriacetic acid, forms a stable Fe-ligand-protein ternary intermediate that slows iron release by introducing a rate-limiting protein conformational change in reaction mechanism. These kinetic studies on iron release from FBP by ligands will contribute to a better understanding of the iron uptake systems mediated by this protein in pathogenic bacteria and aide in the development of potential antibiotic drugs that can block iron uptake.
机译:转铁蛋白超家族包括脊椎动物中的血清转铁蛋白和某些革兰氏阴性病原体中的铁结合蛋白(FBP)。它们都可以可逆地结合铁并在铁的代谢中起重要作用。;关于从血清转铁蛋白释放铁的广泛动力学研究已有报道,但尚未建立详细的铁释放机理。我们的研究集中在pH对几种螯合剂从转铁蛋白中释放铁的两条提议途径的影响上。有关铁释放过程中特定质子化事件的其他信息,已从一些研究中获得,在这些研究中,已采用定点诱变来消除赖氨酸残基,这些赖氨酸残基已被提议充当pH敏感的“触发物”,从而调节调节蛋白质的构象。进行了各种配体从FBP释放铁的动力学研究,并通过光谱法检测了几种短寿命的中间体。提出了铁从该蛋白质释放的一般机制。大多数配体可以非常快速地从蛋白质中去除铁,但是一种配体次氮基三乙酸形成了稳定的Fe-配体-蛋白质三元中间体,通过在反应机理中引入限速蛋白质构象变化来减缓铁的释放。这些有关配体从FBP释放铁的动力学研究将有助于更好地理解在致病细菌中该蛋白质介导的铁吸收系统,并有助于开发可能阻碍铁吸收的潜在抗生素药物。

著录项

  • 作者

    Xiong, Peng.;

  • 作者单位

    University of Missouri - Saint Louis.;

  • 授予单位 University of Missouri - Saint Louis.;
  • 学科 Biochemistry.;Inorganic chemistry.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 144 p.
  • 总页数 144
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 土壤学;
  • 关键词

  • 入库时间 2022-08-17 11:42:10

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