Computer aided comparative analysis of the binding modes of the adenosine receptor agonists for all known subtypes of adenosine receptors.
Molecular models of all known subtypes (A1, A2A, A2B, and A3) of the human adenosine receptors were built in homology with bovine rhodopsin. These models include the transmembrane domain as well as all extracellular and intracellular hydrophilic loops and terminal domains. The molecular docking of adenosine and 46 selected derivatives was performed for each receptor subtype. A binding mode common for all studied agonists was proposed, and possible explanations for differences in the ligand activities were suggested.
Ivanov
Andrei A
AA
Department of Chemistry, M.V. Lomonosov Moscow State University, 119992 Moscow, Russian Federation.
Palyulin
Vladimir A
VA
Zefirov
Nikolai S
NS
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D003196:Computer Graphics; D003198:Computer Simulation; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000737:chemistry* / Q000145:classification / Q000235:genetics; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics; D017386:Sequence Homology, Amino Acid
D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D012243:Rhodopsin; D000241:Adenosine