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

Autor: Amanda Fernandes de Medeiros, Beatriz Blenda Pinheiro de Souza, Lucas Pinheiro Coutinho, Aline Melro Murad, Paula Ivani Medeiros dos Santos, Norberto de Kássio Vieira Monteiro, Elizeu Antunes dos Santos, Bruna Leal Lima Maciel, Ana Heloneida de Araújo Morais
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 480-490 (2021)
Druh dokumentu: article
ISSN: 1475-6366
1475-6374
14756366
DOI: 10.1080/14756366.2021.1876686
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje