title: De novo synthesis and development of an RNA enzyme.
abstract: Arbitrary manipulation of molecular recognition at the atomic level has many applications. However, systematic design and de novo synthesis of an artificial enzyme based on such manipulation has been a long-standing challenge in the field of chemistry and biotechnology. In this report, we developed an artificial RNA ligase by implementing a synthetic strategy that fuses a series of 3D molecular modelings based on naturally occurring RNA-RNA recognition motifs with a small-scale combinatorial synthesis of a modular catalytic unit. The resulting ligase produces a 3'-5' linkage in a template-directed manner for any combinations of two nucleotides at the reaction site. The reaction rate is 10(6)-fold over that of the uncatalyzed reaction with a yield higher than those of previously reported ligase ribozymes. The strategy may be applicable to the synthesis and development of a variety of nonnatural functional RNAs with defined 3D structures.
authors.affiliation: Graduate School of Biostudies, Kyoto University, Kyoto 606-8502, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Ikawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tsuda
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Matsumura
authors.forename: Tan
authors.initials: T
authors.lastname: Inoue
mesh_terms: D001483:Base Sequence; D016384:Consensus Sequence; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011130:RNA Ligase (ATP) / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D011130:RNA Ligase (ATP)