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J Mol Graph Model. 2020 Jan;94:107464. doi: 10.1016/j.jmgm.2019.107464. Epub 2019 Oct 2.

Acetyl-11-keto-β-boswellic acid derivatives effects on 5-lipoxygenase: In silico viewpoint.

Author information

1
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran.
2
Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, Iran. Electronic address: bozorgmehr@mshdiau.ac.ir.

Abstract

The 5-lipoxygenase enzyme is a proinflammatory enzyme and produces leukotrienes. Evidence has shown that inflammation contributes to Alzheimer's disease. On the other hand, boswellic acid derivatives have also been shown to be involved in Alzheimer's disease. In this study, the interaction of four different derivatives of boswellic acid with 5-lipoxygenase enzyme was investigated using molecular dynamics simulation. The simulation of the enzyme was also carried out alone. Calculation of Cα-RMSD indicates that the enzyme stability is slightly affected by boswellic acid derivatives. Calculating the radius of gyration of the enzyme also shows that the overall shape of the protein is not affected by ligands. The RMSF values of the enzyme residues were calculated in the presence of boswellic acid derivatives and it was compared with that in the absence of ligands. The results show that the flexibility of the enzyme residues is influenced by ligands. The residues, whose flexibility is reduced, are scattered throughout the enzyme. However, their number is great in the N-terminal residue. The binding affinity between boswellic acid derivatives and the enzyme residues was calculated using the measure of conformation factor. The results show that the residues interacting with ligands are in the area of the first domain of enzyme. The results obtained from molecular dynamics simulation are well-consistent with the experimental evidence related to the inhibitory effect of the mentioned compounds with 5-lipoxygenase.

KEYWORDS:

Active site; Binding affinity; Boswellic acid; Inhibitor

PMID:
31593921
DOI:
10.1016/j.jmgm.2019.107464

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