Structural insights and molecular dynamics into the inhibitory mechanism of a Kunitz-type trypsin inhibitor from Tamarindus indica L. (1st January 2021)

• Record Type: Journal Article
• Authors: de Medeiros, Amanda Fernandes; de Souza, Beatriz Blenda Pinheiro; Coutinho, Lucas Pinheiro; Murad, Aline Melro; dos Santos, Paula Ivani Medeiros; Monteiro, Norberto de Kássio Vieira; Santos, Elizeu Antunes dos; Maciel, Bruna Leal Lima; de Araújo Morais, Ana Heloneida
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 36:Number 1(2021)
• Page Start: 480
• Page End: 490
• Publication Date: 2021-01-01
• Subjects: Tamarind -- antitryptic -- homology modelling -- computational methods -- protein-protein interaction; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.1080/14756366.2021.1876686
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: Trypsin inhibitors from tamarind seed have been studied in vitro 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 de novo 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.