Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes

Sundlass N.K.; Eller C.H.; Cui Q.; Raines R.T.

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Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes

机译：静电对胰腺型核糖核酸与膜结合的贡献

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Pancreatic-type ribonucleases show clinical promise as chemotherapeutic agents but are limited in efficacy by the inefficiency of their uptake by human cells. Cellular uptake can be increased by the addition of positive charges to the surface of ribonucleases, either by site-directed mutagenesis or by chemical modification. This observation has led to the hypothesis that ribonuclease uptake by cells depends on electrostatics. Here, we use a combination of experimental and computational methods to ascertain the contribution of electrostatics to the cellular uptake of ribonucleases. We focus on three homologous ribonucleases: Onconase (frog), ribonuclease A (cow), and ribonuclease 1 (human). Our results support the hypothesis that electrostatics are necessary for the cellular uptake of Onconase. In contrast, specific interactions with cell-surface components likely contribute more to the cellular uptake of ribonuclease A and ribonuclease 1 than do electrostatics. These findings provide insight for the design of new cytotoxic ribonucleases.

机译：胰腺型核糖核酸酶具有作为化学治疗剂的临床前景，但由于其被人细胞摄取的效率低下而使疗效受到限制。可以通过定点诱变或化学修饰，通过向核糖核酸酶表面添加正电荷来增加细胞摄取。该观察结果提出了这样的假设，即细胞对核糖核酸酶的吸收取决于静电。在这里，我们使用实验和计算方法的组合来确定静电对核糖核酸酶细胞摄取的影响。我们专注于三种同源核糖核酸酶：Onconase（青蛙），核糖核酸酶A（牛）和核糖核酸酶1（人）。我们的结果支持以下假设：静电是细胞摄取Onconase所必需的。相反，与细胞表面成分的特异性相互作用可能比静电对细胞吸收核糖核酸酶A和核糖核酸酶1的贡献更大。这些发现为新型细胞毒性核糖核酸的设计提供了见识。

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《Biochemistry》 |2013年第37期|共9页
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Sundlass N.K.; Eller C.H.; Cui Q.; Raines R.T.;
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support the hypothesis; Contribution of electrostatics; cell-surface;

机译：支持假设;静电的贡献;细胞表面;

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专利

1. Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes [J] . Sundlass N.K., Eller C.H., Cui Q., Biochemistry . 2013,第37期

机译：静电对胰腺型核糖核酸与膜结合的贡献
2. PH DEPENDENCE OF BINDING REACTIONS FROM FREE ENERGY SIMULATIONS AND MACROSCOPIC CONTINUUM ELECTROSTATIC CALCULATIONS - APPLICATION TO 2'GMP/3'GMP BINDING TO RIBONUCLEASE T-1 AND IMPLICATIONS FOR CATALYSIS [J] . Mackerell AD., Karplus M., Sommer MS. Journal of Molecular Biology . 1995,第4期

机译：来自自由能模拟和宏观连续静电计算的结合反应的PH依赖性-应用于核糖核酸酶T-1的2'GMP / 3'GMP结合及其催化意义
3. Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase. [J] . Warshel A, Sharma PK, Chu ZT, Biochemistry . 2007,第6期

机译：静电对过渡态类似物结合的贡献可能与相应的催化作用大不相同：酚盐与酮类固醇异构酶的氧阴离子孔结合。
4. Contribution of Hydrophobic Residues to the Stability of Ribonuclease A Chain Folding Initiation Site Mutants. A Comparison of Pressure and Temperature Induced Unfolding [C] . J. Torrent, J.P. Connelly, M.G. Coll, International conference on high pressure bioscience and biotechnology . 1999

机译：疏水残基的贡献与核糖核酸酶稳定性的链折叠起始位点突变体的贡献。压力和温度诱导展开的比较
5. Electrostatic interactions of biological processes: Cellular internalization of pancreatic-type ribonucleases and salt-bridge formation in a DNA-wrapping protein. [D] . Sundlass, Nadia K. 2011

机译：生物学过程的静电相互作用：胰腺型核糖核酸酶的细胞内在化和DNA包裹蛋白中的盐桥形成。
6. Contribution of Electrostatics to the Binding of Pancreatic-Type Ribonucleases to Membranes [O] . Nadia K. Sundlass, Chelcie H. Eller, Qiang Cui, -1

机译：静电对胰型核糖核酸与膜结合的贡献
7. Electrostatic Contributions to Binding of Transition State Analogues Can Be Very Different from the Corresponding Contributions to Catalysis: Phenolates Binding to the Oxyanion Hole of Ketosteroid Isomerase [O] . -1

机译：与过渡状态类似物的结合的静电贡献可以与对应于催化的相应贡献非常不同：酚类与酮酮异构酶的氧基孔结合

Contribution of electrostatics to the binding of pancreatic-type ribonucleases to membranes

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