Agonistic effect of polyunsaturated fatty acids (PUFAs) and its metabolites on brain-derived neurotrophic factor (BDNF) through molecular docking simulation

Lipids in Health and Disease

Angayarkanni Narayanasamy³  Undurti Narasimha Das¹  Jithu Mohanlal³  Kaviarasan Kuppan³  Sathya Baarathi Ravichandran²  Umashankar Vetrivel² 

[1] Bio-Science Research Centre, Gayatri Vidya Parishad Engineering College, Visakhapatnam, 533 048, India;Department of Bioinformatics, Vision Research Foundation, Chennai, 600 006, India;Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, 600 006, India

关键词: Diabetes;    TrkB;    4-methyl catechol;    LXA4;    BDNF;   

Others  :  1160219
DOI  :  10.1186/1476-511X-11-109

 received in 2012-07-24, accepted in 2012-08-27,  发布年份 2012

【 摘 要 】

Background

Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that is implicated in the regulation of food intake and body weight. Polyunsaturated fatty acids (PUFAs) localised in cell membranes have been shown to alter the levels of BDNF in the brain, suggesting that PUFAs and BDNF could have physical interaction with each other. To decipher the molecular mechanism through which PUFAs modulates BDNF’s activity, molecular docking was performed for BDNF with PUFAs and its metabolites, with 4-Methyl Catechol as a control.

Results

Inferring from molecular docking studies, lipoxin A4 (LXA4), and a known anti-inflammatory bioactive metabolite derived from PUFAs, with a binding energy of −3.98 Kcal/mol and dissociation constant of 1.2mM showed highest binding affinity for BDNF in comparison to other PUFAs and metabolites considered in the study. Further, the residues Lys 18, Thr 20, Ala 21, Val 22, Phe 46, Glu 48, Lys 50, Lys 58, Thr 75, Gln 77, Arg 97 and Ile 98 form hot point motif, which on interaction enhances BDNF’s function.

Conclusion

These results suggest that PUFAs and their metabolites especially, LXA4, modulate insulin resistance by establishing a physical interaction with BDNF. Similar interaction(s) was noted between BDNF and resolvins and protectins but were of lesser intensity compared to LXA4.

【 授权许可】

   
2012 Vetrivel et al.; licensee BioMed Central Ltd.

【 图 表 】

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