title: Binding crevice for TT-232 in a homology model of type 1 somatostatin receptor.
abstract: 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.
authors.affiliation: Department of Neurochemistry, Chemical Research Center, Hungarian Academy of Sciences, Pusztaszeri út 59-67, Budapest H-1025, Hungary. simonagi@chemres.hu
authors.forename: Agnes
authors.initials: A
authors.lastname: Simon
authors.forename: András
authors.initials: A
authors.lastname: Czajlik
authors.forename: András
authors.initials: A
authors.lastname: Perczel
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.forename: Lajos
authors.initials: L
authors.lastname: Nyikos
authors.forename: Zsuzsa
authors.initials: Z
authors.lastname: Emri
authors.forename: Julianna
authors.initials: J
authors.lastname: Kardos
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D003198:Computer Simulation; D016384:Consensus Sequence; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017481:Receptors, Somatostatin / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013004:Somatostatin / Q000031:analogs & derivatives; D014867:Water / Q000737:chemistry*
chemical_list: D046911:Macromolecular Substances; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C101130:somatostatin receptor type 1; D014867:Water; C094462:TT2-32; D013004:Somatostatin; D012243:Rhodopsin