title: Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers.
abstract: Aptamers directed against human thrombin can selectively bind to two different exosites on the protein surface. The simultaneous use of two DNA aptamers, HD1 and HD22, directed to exosite I and exosite II respectively, is a very powerful approach to exploit their combined affinity. Indeed, strategies to link HD1 and HD22 together have been proposed in order to create a single bivalent molecule with an enhanced ability to control thrombin activity. In this work, the crystal structures of two ternary complexes, in which thrombin is sandwiched between two DNA aptamers, are presented and discussed. The structures shed light on the cross talk between the two exosites. The through-bond effects are particularly evident at exosite II, with net consequences on the HD22 structure. Moreover, thermodynamic data on the binding of the two aptamers are also reported and analyzed.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, I-80126 Naples, Italy.|Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone, 16, I-80134 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pica
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, I-80126 Naples, Italy.|Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone, 16, I-80134 Naples, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Russo Krauss
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, I-80126 Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Parente
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Kobe 650-0047, Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Tateishi-Karimata
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Kobe 650-0047, Japan.|Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113- 8656, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nagatoishi
authors.affiliation: Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113- 8656, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20 Minatojima-minamimachi, Kobe 650-0047, Japan sugimoto@konan-u.ac.jp.|Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Via Cintia, I-80126 Naples, Italy filosica@unina.it.|Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone, 16, I-80134 Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Sica
mesh_terms: D052157:Aptamers, Nucleotide / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013816:Thermodynamics; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D013917:Thrombin