Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase

Pharmaceuticals Pub Date : 2024-07-11 DOI:10.3390/ph17070931

Carlos Alberto-Silva, Brenda Rufino da Silva, Julio Cezar Araujo da Silva, Felipe Assumpção da Cunha e Silva, R. Kodama, Wilmar Dias da Silva, M. Costa, F. V. Portaro

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Abstract

Introduction. The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Conclusions. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.

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富脯氨酸十肽的微小结构差异对氧化应激诱导的神经毒性和精氨酸琥珀酸合成酶生成的 L-精氨酸有特定影响

简介。来自两头蛇的富脯氨酸十肽 10c（Bj-PRO-10c；ENWPHPQIPP）能调节精氨酸琥珀酸合成酶（AsS）的活性，从而刺激 L-精氨酸代谢物的产生，并对 SH-SY5Y 细胞系产生神经保护作用。人们对结构、与 AsS 的相互作用以及神经保护之间的关系知之甚少。我们评估了 Bj-PRO-10c 和其他三种 PRO（Bn-PRO-10a、Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a）的神经保护作用。PROs的结构及其与酶活性的相关性显示，Bj-PRO-10c中的组氨酸（H5）和谷氨酰胺（Q7）增强了它们对AsS的亲和力。结论。我们的研究首次揭示了 PROs 的结构及其与 AsS 的分子相互作用，这可能会促进它们在神经药理学方面的应用。

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