Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from <i>Tamarindus indica</i> L

Trypsin inhibitors from tamarind seed have been studied <i>in vitro</i> and in preclinical studies for the treatment of obesity, its complications and associated comorbidities. It is still necessary to fully understand the structure and behaviour of these molecules. We purifed this inhibitor, sequenced <i>de novo</i> by MALDI-TOF/TOF, performed its homology modelling, and assessed the interaction with the trypsin enzyme through molecular dynamics (MD) simulation under physiological conditions. We identified additional 75 amino acid residues, reaching approximately 72% of total coverage. The four best conformations of the best homology modelling were submitted to the MD. The conformation n°287 was selected considering the RMSD analysis and interaction energy (–301.0128 kcal.mol⁻¹). Residues Ile (54), Pro (57), Arg (59), Arg (63), and Glu (78) of pTTI presented the highest interactions with trypsin, and arginine residues were mainly involved in its binding mechanism. The results favour bioprospecting of this protein for pharmaceutical health applications.

罗望子籽来源的胰蛋白酶抑制剂已通过体外（in vitro）实验与临床前研究，被用于肥胖及其并发症与相关合并症的治疗探索。目前仍需全面阐明这类分子的结构与行为特性。本研究纯化了该抑制剂，并通过基质辅助激光解吸电离飞行时间串联质谱（MALDI-TOF/TOF）完成从头测序（de novo）；同时开展同源建模，并在生理条件下通过分子动力学（MD）模拟评估其与胰蛋白酶的相互作用。我们新增鉴定了75个氨基酸残基，序列覆盖度约达72%。选取同源建模得到的4个最优构象进行分子动力学模拟，通过均方根偏差（RMSD）分析与相互作用能（–301.0128 kcal·mol⁻¹）筛选，最终选定构象287。pTTI的异亮氨酸（Ile）54位、脯氨酸（Pro）57位、精氨酸（Arg）59位、精氨酸（Arg）63位以及谷氨酸（Glu）78位残基与胰蛋白酶的相互作用最强，且精氨酸残基主要参与其结合机制。本研究结果为该蛋白在生物医药健康领域的开发应用提供了有力支撑。

搜集汇总

背景与挑战

背景概述

该数据集提供了关于从罗望子种子中提取的Kunitz型胰蛋白酶抑制剂的结构和抑制机制的分子动力学研究数据。它包含通过同源建模和分子动力学模拟获得的蛋白质结构信息，重点分析了与胰蛋白酶相互作用的关键氨基酸残基，旨在支持该蛋白质在药物开发中的应用。数据集包括图像文件和相关元数据，适用于生物物理学、生物化学和药理学领域的研究。