Simon Agnes, Czajlik András, Perczel András, Kéri György, Nyikos Lajos, Emri Zsuzsa, Kardos Julianna
Department of Neurochemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, Budapest H-1025, Hungary.
Biochem Biophys Res Commun. 2004 Apr 16;316(4):1059-64. doi: 10.1016/j.bbrc.2004.02.161.
Somatostatin receptor type 1 was modelled based on the atomic structure of bovine rhodopsin. Possible ways of binding interaction between somatostatin receptor type 1 and TT-232, a cycloheptapeptide analogue of somatostatin with broad therapeutic potential, were analysed by molecular docking. The twelve TT-232 conformations, obtained by NMR measurements in H(2)O-D(2)O mixture, were similar, disclosing a consensus backbone conformation. Several residues interacting with TT-232, such as Val133, Asp137 (helix 3), Arg197 (helix 4), Phe287, Gln291, Asn294 (helix 6), Ser305, and Tyr313 (helix 7), were found. In accordance, in vitro binding experiments indicated high-affinity binding of TT-232 to (125)I labelled somatostatin sites in brain membranes. The single binding crevice obtained by docking may allow the design and discovery of new peptidomimetics of TT-232 in the future.
