Sohail_2014_CNS.Neurol.Disord.Drug.Targets_13_1366

RNA recognition motif (RRM) is the most abundant RNA-binding domain, mainly known to involve in regulating post-transcriptional processes like intron splicing, stability and mRNA intracellular translocation. As RNA metabolism in neurons attributes a significant proportionality towards neurodegenerative diseases, potential role of RRM domains has become more conspicuous. Here, through flexible protein-protein docking and molecular dynamics simulation approaches, we postulate biochemically auspicious interactions occurring between Butyrylcholinesterase (BCHE) and RRM domains of transactive response DNA binding protein, embryonic lethal abnormal vision like protein 4 and heterogeneous nuclear ribonucleoprotein A1 protein. Through a comprehensive analysis of these interactions, we observed an exclusive binding behavior for RRM domains. Evidently, upon binding to RRMs, omega loop of BCHE attains a closed conformation and masks the access of substrate to the catalytic triad and oxyanion hole. Moreover, prominent adjustments were detected in RRM-bound BCHE at the peripheral anionic, choline binding and proton transfer sites. We propose that interaction of RNA-binding proteins to BCHE may decrease its ability to hydrolyze multiple choline esters, which may contribute in delayed progression of poor cognition during neurodegenerative disorders.