Söldner C, Horn A, Sticht H (2018)
Publication Type: Journal article, Original article
Publication year: 2018
Book Volume: 24
Journal Issue: 12
DOI: 10.1007/s00894-018-3873-7
Binding of histamine to the G-protein coupled histamine H-1 receptor plays an important role in the context of allergic reactions; however, no crystal structure of the resulting complex is available yet. To deduce the histamine binding site, we performed unbiased molecular dynamics (MD) simulations on a microsecond time scale, which allowed to monitor one binding event, in which particularly the residues of the extracellular loop 2 were involved in the initial recognition process. The final histamine binding pose in the orthosteric pocket is characterized by interactions with Asp107(3.32), Tyr108(3.33), Thr194(5.43), Asn198(5.46), Trp428(6.48), Tyr431(6.51), Phe432(6.52), and Phe435(6.55), which is in agreement with existing mutational data. The conformational stability of the obtained complex structure was subsequently confirmed in 2 s equilibrium MD simulations, and a metadynamics simulation proved that the detected binding site represents an energy minimum. A complementary investigation of a D107A mutant, which has experimentally been shown to abolish ligand binding, revealed that this exchange results in a significantly weaker interaction and enhanced ligand dynamics. This finding underlines the importance of the electrostatic interaction between the histamine ammonium group and the side chain of Asp107(3.32) for histamine binding.
APA:
Söldner, C., Horn, A., & Sticht, H. (2018). Binding of histamine to the H1 receptora molecular dynamics study. Journal of Molecular Modeling, 24(12). https://dx.doi.org/10.1007/s00894-018-3873-7
MLA:
Söldner, Christian, Anselm Horn, and Heinrich Sticht. "Binding of histamine to the H1 receptora molecular dynamics study." Journal of Molecular Modeling 24.12 (2018).
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