Postgraduate Biochemistry Program, Biosciences Center, Federal University of Rio Grande do Norte, Natal, Brazil.
Postgraduate Biological Molecular, Institute of Biological Sciences, University of Brasília, Brasília, Brazil.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):480-490. doi: 10.1080/14756366.2021.1876686.
Trypsin inhibitors from tamarind seed have been studied 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 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). 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.
从罗望子种子中提取的胰蛋白酶抑制剂已被研究并在临床前研究中用于治疗肥胖症及其并发症和相关合并症。仍有必要充分了解这些分子的结构和行为。我们纯化了这种抑制剂，通过 MALDI-TOF/TOF 进行测序，进行了同源建模，并通过生理条件下的分子动力学 (MD) 模拟评估了与胰蛋白酶的相互作用。我们鉴定了另外 75 个氨基酸残基，达到了总覆盖率的约 72%。最好的同源建模的四个最佳构象被提交给 MD。构象 n°287 是根据 RMSD 分析和相互作用能 (-301.0128 kcal.mol) 选择的。pTTI 的残基 Ile (54)、Pro (57)、Arg (59)、Arg (63) 和 Glu (78) 与胰蛋白酶的相互作用最高，精氨酸残基主要参与其结合机制。这些结果有利于该蛋白的生物勘探，以用于制药健康应用。
