Petrauskas Vytautas, Maximowitsch Eglė, Matulis Daumantas
Department of Biothermodynamics and Drug Design, Institute of Biotechnology, Vilnius University , V. A. Graičiu̅no 8, LT-02241 Vilnius, Lithuania.
J Phys Chem B. 2015 Sep 17;119(37):12164-71. doi: 10.1021/acs.jpcb.5b05767. Epub 2015 Sep 4.
Electrostatic interactions between the positively and negatively charged amino acids in proteins play an important role in macromolecular stability, binding, and recognition. Numerous amino acids in proteins are ionizable and may exist in negatively (e.g., Glu, Asp, Cys, Tyr) or positively (e.g., Arg, Lys, His, Orn) charged form dependent on pH and their pKas. In this work, isothermal titration calorimetry was used to determine the average standard values of thermodynamic parameters (the Gibbs free energy, enthalpy, entropy, and the heat capacity) of interaction between the positively charged amino acid homopolymers (polyarginine, polylysine, and polyornithine) and the negatively charged homopolymers (polyaspartic and polyglutamic acids). These values are of potential use in the computational models of interacting proteins and other biological macromolecules. The study showed that oppositely charged poly(amino acid)s bound each other with the stoichiometry of one positive to one negative charge. Arginine bound to the negatively charged amino acids with exothermic enthalpy and higher affinity than lysine. This result also suggests that positive charges in proteins should not be considered entirely equivalent if carried by lysine or arginine. The difference in binding energy of arginine and lysine association with the negatively charged amino acids was attributed to the enthalpy of the second ionic hydrogen bond formation between the guanidine and carboxylic groups. Despite the favorable enthalpic contribution, all such ion pair formation reactions were largely entropy-driven. Consistent with previously observed ionic interactions, the positive heat capacity was always observed during the amino acid ion pair formation.
蛋白质中带正电荷和负电荷的氨基酸之间的静电相互作用在大分子稳定性、结合和识别中起着重要作用。蛋白质中的许多氨基酸是可电离的，根据pH值及其pKa值，它们可能以带负电荷（如Glu、Asp、Cys、Tyr）或带正电荷（如Arg、Lys、His、Orn）的形式存在。在这项工作中，等温滴定量热法被用于测定带正电荷的氨基酸均聚物（聚精氨酸、聚赖氨酸和聚鸟氨酸）与带负电荷的均聚物（聚天冬氨酸和聚谷氨酸）之间相互作用的热力学参数（吉布斯自由能、焓、熵和热容）的平均标准值。这些值在相互作用的蛋白质和其他生物大分子的计算模型中具有潜在用途。研究表明，带相反电荷的聚（氨基酸）以一正一负电荷的化学计量比相互结合。精氨酸与带负电荷的氨基酸结合时具有放热焓，且亲和力高于赖氨酸。该结果还表明，如果蛋白质中的正电荷由赖氨酸或精氨酸携带，则不应将它们完全视为等同。精氨酸和赖氨酸与带负电荷的氨基酸结合能的差异归因于胍基和羧基之间第二个离子氢键形成的焓。尽管有有利的焓贡献，但所有此类离子对形成反应在很大程度上是由熵驱动的。与先前观察到的离子相互作用一致，在氨基酸离子对形成过程中总是观察到正的热容。
