Characterization of cryptic allosteric site at IL-4Rα: New paradigm towards IL-4/IL-4R inhibition.
作者： Ruqaiya Khalil , Zaheer Ul-Haq , Sehrish Naz , Nida Baig
DOI: 10.1016/J.IJBIOMAC.2018.10.204
关键词:
摘要: Interleukin-4(IL-4), an anti-inflammatory cytokine, plays significant role in pathogenesis of various diseases such as asthma, tumors, and HIV infections. These responses are mediated by expression IL-4R (receptor) on hematopoietic non-hematopoietic cells surfaces. To date, the X-ray crystal structure unbound (i.e. free) is not reported which hampers active research molecular interaction mechanism between IL-4 IL-4R. investigate missing gaps about stable binding mode drug-ability site, modelling dynamics (MD) simulation IL-4/IL-4R complex was performed. Drug-ability target protein changed after loop region near C-terminal protein. This led to identification a novel druggable site other than interfacial site. Our analysis showed that modelled residues Ser111 Ser164-Lys167 part newly discovered allosteric underwent major fluctuation association with its ligand (IL-4). The results indicated possible this cryptic signaling pathway might help us block prevent allergic malignant diseases.
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