COMPUTATIONAL MODELLING OF INTERACTION BETWEEN ISOVALTRATE AND ADENOSINE A1 RECEPTOR

DOI: https://doi.org/10.29296/25877313-2019-09-03
Issue: 
9
Year: 
2019

G.F. Kurakin Resident, Department of Biochemistry and Laboratory Medicine, Tver State Medical University (Tver) E-mail: phyzyk@mail.ru N.P. Lopina Ph.D. (Chem.), Associate Professor, Department of Chemistry, Tver State Medical University (Tver) G.E. Bordina Ph.D. (Biol.), Associate Professor, Department of Chemistry, Tver State Medical University (Tver)

Isovaltrate, a valepotriate contained in valerian roots, is an inverse agonist of adenosine A1 receptor with micromolar affinity. Here, we present results of molecular modelling of its binding to this receptor by flexible docking with Galaxy7TM web server. We modelled isovaltrate binding to human and rat adenosine A1 receptor. The modelling has shown that isovaltrate mimics xanthine antagonists upon binding to adenosine A1 receptor. It occu-pies similar position and forms analogous interactions: hydrogen bond with Asn254 and hydrophobic contacts with Phe171, Leu250, Ile274. Despite lacking aromatic structure, bicyclic core formed vast hydrophobic interactions with Phe171 positioning itself similar to xanthine and flavonoid core. Other studied valepotriates, valtrate and deacetylisovaltrate, were unabe to fully mimic there interactions. We proposed that xanthine, flavonoid and isovaltrate binding is provided by common structural features: flat or almost flat bicyclic core, hydrogen bond acceptor attached to it and side chains. Obtained modelling data can be used for designing new adenosine receptor blockers and sedative drugs.

Keywords: 
isovaltrate
valepotriates
valerian
adenosine receptors
computational modelling

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